OBJECTIVES: We examined the prognostic implications of the absolute level and rate of increase of creatine kinase (CK) elevation after primary percutaneous coronary intervention (PCI). BACKGROUND: Peak creatine kinase (CKpeak) and the rate of CK increase are related to reperfusion success and clinical outcomes after thrombolytic therapy for acute myocardial infarction (AMI). The utility of routine serial CK monitoring after primary PCI, in which normal antegrade blood flow is restored in most patients, is unknown. METHODS: In the Controlled Abciximab and Device Investigation to Lower Late Angioplasty Complications (CADILLAC) trial, 1,529 patients with AMI randomized to either stenting or balloon angioplasty, each with or without abciximab, had CK levels determined at baseline and at 8 ± 1 h, 16 ± 1 h, and 24 ± 1 h after PCI. RESULTS: The CKpeak occurred at baseline in 3.9% of patients, at 8 ± 1 h in 69.6%, at 16 ± 1 h in 20.0%, and at 24 ± 1 h in 6.5%. The CK levels at all post-procedural time points were significantly higher in patients who died compared with the one-year survivors, as was CKpeak (mean, 2,865 U/l vs. 1,885 U/l, respectively, p ≤ 0.001). By multivariate analysis, CKpeak was a significant predictor of one-year mortality (hazard ratio = 2.15, p = 0.0002), independent from post-PCI Thrombolysis In Myocardial Infarction (TIMI) flow. Both the improvement in left ventricular ejection fraction from baseline to seven months and its absolute level were inversely correlated with CK peak (p < 0.001 for both). In contrast, the time to CK peak was not an independent predictor of mortality or myocardial recovery. CONCLUSIONS: The CKpeak after primary PCI is a powerful predictor of one-year mortality independent of other clinical and angiographic measures.