This auspicious debut was followed by the less inspired "Johnny Dangerously" (1984), a scattershot spoof of 1930s gangster movies starring Michael Keaton. Heckerling fared better commercially with the broad antics of "National Lampoon's European Vacation" (1985). Though uneven, this sequel to 1983's "National Lampoon's Vacation" was a box-office hit. No one expected the huge success of her next feature, "Look Who's Talking" (1989). This genial romantic comedy employed the engaging gimmick of broadcasting a baby's thoughts in voice-over, a gag later varied and recycled for two sequels. Heckerling served as writer-director on the first two films and segued to producing with the third. She also made Kirstie Alley into a movie star of sorts and provided the then former superstar John Travolta with steady work. This unpretentious comedy franchise also generated a fleeting TV series, "Baby Talk" (ABC, 1991-92), for which Heckerling received a creator's credit. Previously, she had worked in TV in the mid-80s as a producer and occasional writer and director on such efforts as "Fast Times" (CBS, 1986), the short-lived TV version of her breakthrough feature, and "Tough Cookies" (CBS, 1986), a cop sitcom.
Following the "Look Who's Talking" trilogy, Heckerling returned to high school to research her next project "Clueless" (1995), a smart satirical look at the lives of affluent Beverly Hills teens. The writer-director hung out with real students so as the capture the nuances of their up-to-date lingo before deploying them in a story that owed much to Jane Austen's novel "Emma". The film opened to generally favorable reviews and a healthy box office, won Heckerling Best Screenplay honors from the National Society of Film Critics, and became a classic in the teen film genre. The spin-off series ("Clueless", 1996-1999) spent a season on ABC before moving to UPN, and Heckerling was credited as creator and executive producer. She also contributed to the sitcom as an occasional writer and director. Her next film project was 1998's "A Night at the Roxbury", which she had a hand in as a producer. Based on unlucky in love nightclubbing brothers from an inane recurring "Saturday Night Live" sketch, the film didn't impress many critics or moviegoers. Heckerling followed up as executive producer of the disappointing "Molly" (1999), an Elisabeth Shue starrer about a developmentally disabled woman.
In 2000, Heckerling seemed poised to reclaim the sleeper glory of "Clueless" with the charming underdog comedy "Loser", a New York University-set feature starring hot tickets Jason Biggs (playing Paul, a sheltered Midwesterner) and Mena Suvari (as Dora, a coed with a crush on her professor). Heckerling was able to draw somewhat on her own experiences with this film, dealing with outcasts in Manhattan as opposed to the beautiful youth of Southern California that had launched ("Fast Times at Ridgemont High") and then solidified ("Clueless") her career.