We report on 348 patients≥70 years (median age 78 years) with acute myeloid leukemia (>50% with secondary AML) randomized to receive either 600mg or 300mg of tipifarnib orally twice daily on days 1-21 or days 1-7 and 15-21, repeated every 28 days (4 treatment regimens). Responses were seen in all regimens, with overall response rate (CR+CRi+PR) highest (20%) among patients receiving tipifarnib 300mg twice daily on days 1-21. Toxicities were acceptable. Unless predictors of response to tipifarnib are identified, further study as a single agent in this population is unwarranted.