Infarct size after ST-segment elevation myocardial infarction (STEMI) is associated with long-term clinical outcomes. However, there is insufficient information correlating creatine kinase-MB (CK-MB) or troponin levels to infarct size and infarct location in first-time occurrence of STEMI. We, therefore, assessed the utility of CK-MB measurements after primary percutaneous coronary intervention of a first anterior STEMI using bivalirudin anticoagulation in patients who were randomized to intralesion abciximab versus no abciximab and to manual thrombus aspiration versus no aspiration. Infarct size (as a percentage of total left ventricular [LV] mass) and LV ejection fraction (LVEF) were evaluated by cardiac magnetic resonance imaging at 30 days and correlated to peak CK-MB. Peak CK-MB (median 240 IU/L; interquartile range 126 to 414) was significantly associated with infarct size and with LVEF (r = 0.67, p <0.001; r = −0.56, p <0.001, respectively). A large infarct size (greater than or equal the median, defined as 17% of total LV mass) and LVEF ≤40% were more common in the highest peak CK-MB tertile group than in the other tertiles (87.6% vs 49.5% vs 9.1%, p <0.001; 43.2% vs 14.0% vs 4.6%, p <0.001, respectively). Peak CK-MB of at least 300 IU/L predicted with moderate accuracy both a large infarct size (area under the curve 0.88) and an LVEF ≤40% (area under the curve 0.78). Furthermore, CK-MB was an independent predictor of 1-year major adverse cardiac events (hazard ratio 1.42 per each additional 100 IU/L [1.20 to 1.67], p <0.001). In conclusion, CK-MB measurement is useful in estimating infarct size and LVEF and in predicting 1-year clinical outcomes after primary percutaneous coronary intervention for first anterior STEMI.