Plasma fibrinogen, C-reactive protein (CRP), and interleukin-6 (IL-6) levels in patients with acute myocardial infarction (AMI) receiving thrombolysis have been related to prognosis. The aim of this study was to investigate the time course of plasma fibrinogen, CRP, and IL-6 levels during the in-hospital phase in patients with AMI receiving thrombolysis, and their relationship to in-hospital and prognosis after 12-months follow-up. In 40 patients presenting with AMI within 6 hours of symptom onset and treated with thrombolysis, plasma fibrinogen, CRP, and IL-6 levels were measured on admission and after 6, 12, 24, 48, and 72 hours; 7 days; and 6 months. Patients with other diseases that can alter fibrinogen, CRP, or IL-6 levels were excluded. Patients had a clinical follow-up at 6 and 12 months, and the following cardiac events were recorded: cardiac death, recurrent angina, recurrent AMI, and heart failure. Plasma fibrinogen concentrations decreased significantly (p <0.01 vs admission levels) at 12 hours (425 ±94 vs 322 ±132 mg/dL), started to increase at 24 hours, reached peak value at 72 hours (602 ±209 mg/dL), remained elevated at 7 days, and were back to admission levels at 6 months (375 ±79 mg/dL). CRP levels increased significantly at 12 hours (0.73 ±0.43 vs 0.23 ±0.11 mg/dL, p <0.01), reached peak value at 72 hours (7.66 ±3.28 mg/dL), decreased significantly on day 7 (2.32 ±1.17 mg/dL), and at 6 months were within normal limits (0.49 ±0.29 mg/dL). IL-6 levels increased significantly at 6 hours (14.03 ±8.13 vs 6.37 ±3.88 pg/mL, p <0.05), reached peak value at 24 hours (59.49 ±23.57 pg/mL), started to decrease at 48 hours, and at 6 months were within normal limits (2.25 ±1.24 pg/mL). During the in-hospital phase 33 patients had an uneventful course and 7 patients had complications (3 post-AMI angina; 4 heart failure). During the 12-month follow-up period 28 patients had an uneventful course, and 12 patients had complications (1 cardiac death, 5 recurrent angina, 2 recurrent AMI, and 4 heart failure). Regarding the in-hospital prognosis, fibrinogen, CRP, and IL-6 levels were significantly higher (p <0.05) in patients with complications from 48 to 72 hours, from 12 hours until day 7, and from 6 hours until day 7, respectively. During the 12-month follow-up period fibrinogen, CRP, and IL-6 levels were significantly higher in patients with complications (at 48, 24, and 24 hours, respectively) only in the subgroup of patients who had complications within the first 6 months following AMI. Multivariate analysis showed that CRP at 48 hours was the most important factor related to in-hospital prognosis (p = 0.02), and ejection fraction followed by CRP at 24 hours (p = 0.02) to 6-month prognosis (p = 0.018). Fibrinogen, CRP, and IL-6 levels alter in patients with AMI receiving thrombolysis, and are related both to in-hospital and to 6-month follow-up prognosis.