Draw back the curtains on this weekend’s Bentzen Ball Comedy Festival, and you’ll find Tig Notaro, official festival string-puller.

The District-born festival, back for a second run after a four-year hiatus, will bring in a wave of comedy up-and-comers, television stars and underground oddballs to five D.C. venues, including the Lincoln Theatre, Howard Theatre and the 9:30 Club, through Sunday. And it’s Notaro, a shaggy-haired, flannel-favoring comedian with a reassuring tone, who calls in the talent, tapping a mind-boggling clique of famous funnymen and women who use words such as “cherish” to describe their friendships with the 42-year-old.

For this year’s Ball, hosted by culture Web site Brightest Young Things, Notaro has recruited Megan Mullally of “Will & Grace” and “Parks and Recreation” fame; Wyatt Cenac, best known for his years as a correspondent on “The Daily Show”; Nick Kroll of Comedy Central’s “The Kroll Show”; and “Saturday Night Live” alum Rachel Dratch, among others. Notaro herself will make appearances throughout the event, including an opening-night stand-up performance Thursday at the 9:30 Club.

“I was just blown away by Tig,” Mullally says of the first time she saw Notaro perform. “She’s so unique, and her humor is so smart and so spare. It doesn’t hurt when a few of your friends are full-on geniuses, and I would consider her one.” When Notaro asked Mullally to be part of the festival with her musical duo, Nancy & Beth, Mullally says she couldn’t say no.

Chatting recently over a video call from Los Angeles, Notaro is jokingly apologetic that she might be the only comic to play the Bentzen Ball twice. As curator, she wanted the lineup to be different from four years ago, to give new comedians a chance to perform for Washington audiences. The intervening years, however, have transformed Tig Notaro. This time, she’s one of the biggest names on the bill.

Notaro’s star was already rising in 2009, when she helmed the first Bentzen Ball. She was widely considered a favorite of comedians who appreciate the craft. But just over a year ago, after going through a breakup, a nearly fatal bacterial infection and the loss of her mother in a freak accident, Notaro took the stage at Largo, the legendary Los Angeles comedy club, and, palpably shell-shocked, revealed another personal tragedy.

“Good evening, hello,” she said. “I have cancer. How are you?”

Notaro continued for a half-hour, describing the most tragic days of her life to an audience that laughed with her, because, well, what else could they do? The next day, her pal Louis C.K., who was backstage that night, tweeted to his million-plus followers: “In 27 years doing this, I’ve seen a handful of truly great, masterful standup sets. One was Tig Notaro last night at Largo.” The recording of that night’s set, “Live,” sold more than 100,000 copies and landed on the top of every important comedy best-of list last year.

Based 2,600 miles away in Los Angeles, Notaro is an unlikely partner for the D.C.-based Brightest Young Things. When she performed in Washington in 2008, she was interviewed by BYT writer Jeff Jetton and mentioned wanting to organize her own festival. New York and Los Angeles have many comedy festivals; the District not so much. Intrigued, Jetton roped in his friends at the Web site to create one.

For the first festival, Notaro called on such comedians as Lizz Winstead, Sarah Silverman and Reggie Watts. BYT, then mostly 20-something event-throwing neophytes, booked venues, printed T-shirts, made airport pickups and crossed their fingers.

Notaro made the Bentzen Ball what the performers began calling “comedy camp.” She and 30 comedians rolled past the White House and other sites on one very funny Segway tour, ate pizza and had a champagne and cupcake brunch. The comedians, in turn, killed.

Today, Notaro is a little more gray around the temples, a little more lean than the sprite in the pink T-shirt who gleefully parted the crowd at a sold-out 9:30 Club four years ago. It was there, as she and longtime pal Silverman gave the first Bentzen Ball a sweaty rock-show send-off, that Washington’s appreciation for Notaro’s dry, soothingly delivered humor seemed to crystalize. She worked the room, eliciting confessions about debt and strained friendships and drawing sympathetic belly laughs from the crowd.

That’s the power of Notaro’s humor. She doesn’t hang old girlfriends or family members out to dry. Or harp about long lines at the grocery store or how smartphones are turning our brains to mush. Her insights about life can be cutting, sad, funny. And if you’re not laughing at yourself, you’re not listening.

“There’s a certain confidence that she has as a performer that is so unbelievably engaging to watch,” says Kroll, who has known Notaro for more than a decade and who will perform Saturday. “I love D.C. and always relish the chance to come back and perform, but if Tig had asked me to go to Greenland, I would have gone.”

There’s no singular explanation for the four-year gap that followed that wild night at the 9:30 Club. The Bentzen Ball was BYT’s first big multi-venue event, and it lost what Jetton describes as a negligible amount of money. Mostly, he says, it was a “very, very stressful weekend. There was no learning curve. It left everyone exhausted emotionally.”

In the interim, Notaro won a role playing mom to Kristen Stewart’s young Joan Jett in the movie “The Runaways,” (she ultimately didn’t make it into the movie), and began touring heavily. After her breast cancer diagnosis, Notaro had a double mastectomy (she’s now in remission). Last fall, Jetton met with her, and the two finally broached the idea of doing the festival again.

This time, Notaro had to set aside a slew of other projects to take on the Ball: the book she is writing about her hell year, the documentary that’s being shot about her life. She tours with her science-meets- comedy podcast, “Professor Blastoff,” which this spring filled the Sixth & I Historic Synagogue to capacity and then some. Her career has been injected with a new energy, a fact that she says has everything to do with her illness.

“I can’t take away the fact that I had cancer,” Notaro says. “I feel lucky that I had cancer, as odd as that may sound. I describe it as teetering on this edge that you can’t just walk up to. You are teetering on this edge, and someone yanked me back.

“The view that I got to see from the edge, I could not have that view, and that perspective. I can’t imagine it not being a part of my life. I can’t see it as a negative.”