On January 1, 1991, Tartikoff and his daughter Calla were involved in a near fatal car accident. While he recovered fairly quickly, his daughter had been severely injured and required extensive treatment for her injuries. The family relocated to New Orleans to facilitate her therapy. Nevertheless, Tartikoff accepted the position of chairman of Paramount Pictures but, citing family obligations, resigned abruptly in October 1992. During his brief tenure at the studio's helm, Paramount had box-office successes as "Wayne's World" and "Patriot Games" but also released such disappointments as "Coneheads" and "Leap of Faith".
After a two year absence from the industry, Tartikoff returned as chairman of New World Entertainment, signing a five year contract and selling his company Moving Target Productions for $9 million to his new employer. His tenure, however, lasted only about two years when New World was sold to Rupert Murdoch's News Corporation of America. Tartikoff moved into independent production, forming The H. Beale Company. In March 1997, he became chairman of Greenhouse Networks, a content provider for American Online. Having been battling Hodgkin's disease since age 25, Tartikoff succumbed to the cancer in August 1997 at age 48.