The difficulty involved in recruiting healthy older adults into clinical trials, especially those involving pharmacologic agents, is an important issue in research. The Ginkgo Evaluation of Memory (GEM) Study, a double-blind, placebo-controlled randomized clinical trial evaluating Ginkgo biloba to prevent dementia, successfully recruited 3072 participants age 75 years and older at four U.S. sites from September 2000 through June 2002. Using targeted mailing lists, an estimated 243,400 study brochures were mailed out to potential participants. Subsequent attempts were made to reach 14,603 households by telephone, from which 12,186 (83.4%) successful contacts were made. Overall, telephone or in-person evaluations identified 2149 (17.6%) ineligible persons for cognitive (20.6%), medical (49.4%), or other (30.0%) reasons. A total of 6944 (57.0%) refused participation resulting in 3072 enrolled into the study, a recruitment rate of 25.2% based on telephone contacts made or 1.3% of all mailed brochures. Recruitment rates were stable over the 21-month enrollment period but were higher for the two urban centers than the two rural ones. Recruitment was dependent most on mailing lists available, density of older adults in the catchment areas, and Institutional Review Board restrictions. Men and persons under age 85 were more likely to enroll. Primary reason for refusals involved lack of interest (48.4%) or self-perceived poor health (16.2%). Over 9% were unwilling to give up current Ginkgo supplementation or would not accept assignment to placebo. An additional 7% did not want another medication and almost 4% had care-giving responsibilities which prevented involvement. Mass mailings were the most successful approach for recruitment at all four sites and the method through which the vast majority of interviewees had learned about the study. Information on the experience of the GEM Study recruitment may be helpful to other clinical trials attempting to randomize older adults into prevention trials.