Thrombolytic therapy decreases the mortality rate in patients with acute myocardial infarction (AMI), and the timing of thrombolysis has proved to be critical for decreasing the short-term mortality rate. Much less is known about the longer term consequences of delays in thrombolysis, particularly for outcomes other than the mortality rate. We assessed the effect of time to thrombolysis and other clinical predictors on cardiac functional status 6 months after AMI. We used InTIME II, a multicenter trial, to test the efficacy of alteplase and lanoteplase. This component of the trial was conducted in 147 North American centers. Patients were > or =18 years of age with ST-elevated AMI. Functional status was measured by the Duke Activity Status Index, which was administered 6 months after AMI. After multivariate adjustment for baseline characteristics, delay in presentation to hospital and delay in initiation of thrombolysis were significantly and independently associated with decreased cardiac functional status 6 months later. Each additional hour from symptom onset to hospital presentation was associated with a 16% increase (95% confidence interval 3% to 31%) in the likelihood of functional impairment (Duke Activity Status Index score < or =30). In addition, each additional delay of 1 hour from hospital presentation to thrombolysis independently increased the probability of functional impairment by 38% (12% to 71%). Thus, in patients with AMI, earlier presentation to the hospital and more rapid initiation of thrombolysis could prevent significant decreases in functional status months after the initial infarct.