Objective: It was the aim of this study to document the risks of symptomatic patients with angina in placebo-controlled, anti-anginal drug development trials in which symptom-limited exercise testing was used as the primary endpoint. Patients and Methods: The original case report forms submitted to the United States Food and Drug Administration in support of approval of new or supplemental new drug applications between 1973 and 2001 were identified and subjected to a by-patient meta-analysis, utilizing both a maximum likelihood analysis and classical Mantel-Haenszel methods. Results: There were 63 placebo-controlled, clinical trials that randomized 10,865 patients, with 1,047 patient-years of observation time. The trials involved 21 different chemical entities from 4 different drug classes. The relative risk (RR) for withdrawal (placebo compared to drug-treated patients) was not increased [RR = 0.92, 95% confidence interval (CI) 0.78-1.08; p = 0.28]. Of interest, a RR of 0.54 (95% CI 0.26-1.04; p < 0.068) for irreversible harm (a combination of cerebrovascular accidents, myocardial infarction and death) and a RR of 0.89 (95% CI 0.61-1.30; p = 0.56) for serious cardiovascular events (myocardial infarction, congestive heart failure, cerebrovascular accidents) both non-statistically significantly favored being randomized to placebo. Conclusions: For the development of current or future drugs for the treatment of angina, there is no obvious contraindication to the use of placebo controls and exercise tolerance testing. © 2012 S. Karger AG, Basel.