The relative accuracy of randomized control trials (RCTs) and historical control trials (HCTs) in determining effective therapies has not been compared since there is no external verification of efficacy. We reviewed six therapies studied by both methods. Most HCTs concluded therapy was better than control, but few RCTs agreed. We calculated sensitivity and specificity for each type of trial by combining published results with all possible combinations of effectiveness. The sensitivity of HCTs was 0.80 to 1.00 (mean, 0.90) and specificity was 0.0 to 0.27 (mean, 0.11). The sensitivity of RCTs was 0.0 to 0.27 (mean, 0.12) and specificity was 0.67 to 1.00 (mean, 0.88). Defects of RCTs are more easily corrected than those of HCTs. Readers should consider trial design and the probability of errors when deciding how much credence to give to a clinical trial.