The prognostic role of C-reactive protein levels in patients with a first acute myocardial infarction, an uncomplicated in-hospital course, and the absence of residual ischemia on a predischarge ergometer test and with an echocardiographic ejection fraction > or = 50% has not been described. C-reactive protein was determined during hospitalization in 64 patients (55 men, mean age 64.6 +/- 10.4 years). The patients were followed up for 13 +/- 4 months and the following cardiac events were recorded: cardiac death, new-onset angina pectoris, and recurrent myocardial infarction. Patients who developed cardiac events during the follow-up period had significantly higher C-reactive protein values than patients without events (3.61 +/- 2.83 vs 1.48 +/- 2.07 mg/dl, p <0.001). The probability of cumulative end points was: 6%, 12%, 31%, and 56% (p = 0.006; RR 3.55; confidence interval 1.56 to 8.04), respectively, in patients stratified by quartiles of C-reactive protein (< 0.45, 0.45 to 0.93, 0.93 to 2.55 and > 2.55 mg/dl). In the Cox regression model, only increased C-reactive protein levels were independently related to the incidence of subsequent cardiac events (chi-square 9.8, p = 0.001). Thus, increased C-reactive protein levels are associated with a worse outcome among patients with a first acute myocardial infarction, an uncomplicated in-hospital course without residual ischemia on the ergometer test, and with normal left ventricular function.