Several angiographic adverse events during coronary balloon angioplasty have been associated with increased creatine kinase-MB (CK-MB) enzymes and adverse clinical outcomes. The significance of angiographic adverse events in the stent era has not been widely studied. We analyzed 10 types of angiographic adverse events that were reported in the 6,010-patient Second Randomized Evaluation in PCI Linking Angiomax to Reduced Clinical Events (REPLACE-2) trial to determine their relation to CK-MB elevation and clinical ischemic end points after percutaneous coronary intervention (PCI). Angiographic adverse events occurred in 9.1% of REPLACE-2 patients. Most (8 of 10) types of angiographic adverse events were associated with an increased risk of increased CK-MB (p <0.001 for each), and 47% of all patients with an angiographic adverse event developed increased CK-MB. Logistic regression analysis showed that the strongest predictor of death, myocardial infarction, or revascularization at 6 months was the occurrence of an angiographic adverse event during PCI (odds ratio 1.9, 95% confidence interval 1.6 to 2.4, p <0.001). Side branch closure, abrupt closure, any decreased flow during the procedure, angiographic distal embolization, and perforation or tamponade were individual predictors of the occurrence of the combined clinical ischemic end point at 6-month follow-up (p <0.005 for each). In conclusion, most angiographic adverse events during PCI are associated with increased CK-MB and are powerful predictors of adverse clinical events within 6 months.