Two categories--patients alive and free from new myocardial infarction (MI) and time to first new MI (nonfatal and fatal)--were compared in medical and early surgical groups in the Coronary Artery Surgery Study (CASS) registry with Class I or II angina and three-vessel disease in a six-year follow-up. There were 413 in the medical group and 443 in the early surgical group. A broad definition of MI using ECG and clinical criteria on hospital discharge and follow-up was used to include as many new MIs as possible, including perioperative MIs. Stratification was by left ventricular wall motion score and number of proximal segment stenoses and by quintile of propensity score to reduce selection bias in therapy groups. Adjusted by propensity analysis, 79% of medical and 88% of surgical patients (p = .005) were free from new MI; death without diagnosis of new MI was censored. Similarly adjusted, 57% of medical and 76% of surgical patients (p less than .0001) were alive and free from new MI at six years. For patients with previous MI, surgery offered the probability of protection from new MI: with multiple prior MIs, 66% of medical and 88% of surgical patients were free from new MI at six years (p = .0019). This is a nonrandomized, observational study with the limitations of such studies: the need to adjust for differences in baseline traits in medical and surgical groups and the unknown effects of unobserved variables. Fifty-one variables, including therapy, were tested by Cox model with time to new MI as the end point. Early surgery was the strongest independent predictor of freedom from new MI (p = .002) with a relative risk of 51% compared with medical therapy (95% confidence limits of 33 to 78%). In patients with multiple prior MIs, the new MI risk with early surgery was 24% of that for medicine, with an upper 95% confidence point of 64%.