This protocol describes the design of an international study to examine the potential prophylactic effect of 14 days of diltiazem therapy to prevent early reinfarction in patients initially presenting with non-Q-wave acute myocardial infarction. Reinfarction was defined by the detection of a secondary elevation of plasma MB-creatine kinase. The results of clinical trials, instrumental in this protocol design, that established the increased propensity for early reinfarction after initial non-Q-wave infarction are described and the implications of the present study are discussed.