We aimed to describe enrollment patterns in a large cohort of randomized controlled trials (RCTs) and evaluate whether early recruitment predicts the ability of RCTs to reach their target enrollment. We considered all 77 efficacy RCTs initiated by the AIDS Clinical Trials Group between 1986 and 1996 (28,992 patients enrolled until November 1999). Thirteen RCTs (17%) failed to reach half their target recruitment. Enrollment trajectories showed that the initial rate of accrual determined the subsequent rates of enrollment. The target sample size was attained by 7/8, 11/14, 15/35 and 4/20 of trials with very rapid, rapid, moderate and slow enrollment during the first 3 months, respectively (P < 0.001). Enrollment during the first month or two strongly correlated with subsequent accrual (P < 0.001). The patient pool, the eligibility criteria, the attractiveness of a trial and adequacy of the network of clinical sites may influence RCT enrollment. Early enrollment offers strong evidence on the feasibility of a trial and is indicative of its future pace of recruitment.