Background Secondary coronary prevention studies have generally focused on specific medications, often to the exclusion of commonly used therapies. To date, long-term nitrate use has not been investigated in large-scale clinical trials. Methods and Results We examined the relation between long-acting nitrates given during the chronic phase of the disease and the outcome. We analyzed data prospectively acquired in a large, observational study involving 1042 patients enrolled for the Multicenter Study of Myocardial Ischemia (MSMI) in North America, Israel, and Japan as well as 1779 patients enrolled for the Multicenter Diltiazem Post Infarction Trial (MDPIT). The Cox analyses with all the variables retained revealed that nitrates were associated with a significantly increased mortality risk (MSMI: hazard ratio 3.78, P = .011; MDPIT: hazard ratio 1.61, P = .019) in patients who had recovered from an acute coronary event. The analyses with the propensity score method on the MSMI and the MSMI databases also showed that the risk for cardiac death with use of nitrates was increased in most of the 5 subclasses according to the score. Conclusion These analyses raise concern about the potential adverse effects of long-acting nitrate therapy in chronic coronary disease. (Am Heart J 1999;138:577-85.)