Angiographically documented coronary artery disease (CAD) can progress. Although progression itself is frequently recognized in patients who have undergone repeat cardiac catheterization, its prognostic significance remains unclear. To evaluate the influence of progression on survival, 313 patients with CAD who underwent catheterization twice (39 +/- 25 months apart) were followed for 3 to 129 months (mean 41 +/- 30) after the second angiogram. At the time of the second angiogram, 21, 91, 113 and 88 patients had 0-, 1-, 2- and 3-vessel CAD, respectively. The mean ejection fraction (EF) of the group was 55 +/- 13%. Progression was noted in 139 patients (44%). Of the 313 patients, 33 died and 39 had acute myocardial infarction (AMI) during follow-up. Four-year survival was estimated at 94% and 83% in the nonprogression and progression groups, respectively. Progression was predictive of survival by (univariate) long-rank test (p less than 0.01), but only EF (p less than 0.001), number of diseased vessels (p less than 0.01) and percent stenosis in the left main coronary artery (p less than 0.05) were independently significant by (multivariate) Cox regression analysis. Four-year survival without AMI was 89% and 73% in the nonprogression and progression groups, respectively. Progression was related to survival without AMI (p less than 0.001) by log-rank test. Cox regression analysis provided 3 independent predictors of survival without AMI: number of diseased vessels (p less than 0.01), progression (p less than 0.01), relative risk = 2.28) and EF (p less than 0.01). Results were similar when analyzing only the 39 AMIs.(ABSTRACT TRUNCATED AT 250 WORDS)