A central requirement for epidemiologic studies and clinical trials is a bias-free, objective determination of cardiac incidence rates between comparison groups. Epidemiologic studies and clinical trials frequently use changes in the Minnesota Code to document incident ischemic events. An electrocardiographic (ECG) classification system was developed to document significant ECG pattern change using objective comparison rules for side-by-side annual ECG comparison. Previously, we showed that major evolving Q waves were strongly and independently associated with total and coronary disease mortality. Using baseline-to-annual ECG comparisons in the Multiple Risk Factor Intervention Trial, we evaluated major evolving Q waves, minor evolving Q waves combined with major evolving ST-T waves and major evolving ST-T waves alone for their prognostic associations with coronary, cardiovascular, and total mortality during 16 years of follow-up. The 16-year coronary mortality rate in men with evolving minor Q waves plus evolving ST-T waves had an average adjusted relative risk of 4, equivalent to that of a major evolving Q wave. These risk ratios held whether a clinical infarction had occurred. Silent evolving ST-T waves without Q-wave change had an average adjusted relative coronary mortality risk of 1.6. Serial comparison methodology documents additional incident ischemic ECG events beyond the traditional major Minnesota Q-code change used in older epidemiologic studies. The procedure is standardized, quantitative, and repeatable. It is applicable for any study, present or past, that used Minnesota coding. The method is also well suited for incorporation in computer analysis programs.