Background The clinical significance of minor elevations in creatine kinase-myocardial band isoenzyme (CK-MB) after coronary interventions has not been systematically evaluated. Methods and Results We examined 4484 patients who underwent successful percutaneous transluminal coronary angioplasty or directional coronary atherectomy and whose peak CK levels did not exceed twice the upper limit of laboratory normal. Group 1 (3776 patients) had no CK or MB elevation after the procedure (ie, CK less than or equal to 180 IU/L, with MB fraction less than or equal to 4%). Group 2 (450 patients) had a peak CK level between 100 and 180 IU/L, with MB fraction >4%, and group 3 (258 patients) had a peak CK level between 181 and 360 IU/L, with MB fraction >4%. The strongest correlate of postprocedure CK-MB elevation was the performance of directional coronary atherectomy (odds ratio, 4.1; P<.0001), followed by the development of greater than or equal to 1 in-lab minor procedural complication (odds ratio, 2.6; P<.0001). Clinical follow-up was available in 4461 patients (99.5%), with a mean duration of 36 +/- 22 months. Survival analysis, adjusted with Cox proportional hazards regression model, showed that the groups with elevated CK-MB had a significantly higher incidence of cardiac death (risk ratio, 1.3; P=.04) and myocardial infarction (risk ratio, 1.3; P=.03). Major ischemic complications (death, myocardial infarction, and coronary revascularization) occurred more frequently in the groups with increased CK-MB (groups 1 versus 2 versus 3, 37.3% versus 43.3% versus 48.9%; P=.01). Conclusions This study shows that minor elevations of CKMB after successful coronary interventions identify a population with a worse long-term prognosis compared with patients with no enzyme elevations and appear to have an adverse effect on long-term prognosis. Future studies of percutaneous coronary revascularization should include routine measurements of biochemical cardiac markers as important predictors of long-term prognosis.