This study sought to determine the long-term prognostic significance of persistent or transient negative T waves in infarct-related leads. After acute myocardial infarction (AMI), QRS and T wave alterations may resolve. No clinical study has investigated the prognostic importance of persistent versus transient negative T waves. We studied 147 consecutive patients with first AMI and >/=2 negative T waves in the infarct-related leads on the electrocardiogram. One hundred twenty patients developed Q waves. Patients were followed clinically for 60 +/- 21 months. T-wave normalization was observed early (before hospital discharge) in 34 patients and late (at 4 +/- 1 months) in 65. Thirty patients had Q-wave regression. Adverse outcome occurred in 57 patients. There were 23 hard events (cardiac death in 12 patients and nonfatal AMI in 11). Patients with early or late T-wave normalization had similar event-free survival curves that diverged rapidly from that of patients with persistent negative T waves, who had a worse outcome (p <0.0001). Patients with or without Q-wave regression had similar survival curves. Using multivariate Cox regression analysis, higher end-systolic volume (hazard ratio [HR] 1.01, p = 0.007), the presence of multivessel disease (HR 3.33, p = 0.009), and persistent negative T waves (HR 2.92, p = 0.024) predicted hard events. Persistent negative T waves 4 months after first AMI were independently associated with a worse outcome, whereas Q-wave regression has no long-term prognostic importance.