Objective: To investigate the prognostic value of serum copeptin level combined with thrombolysis in myocardial infarction (TIMI) score in patients with acute STsegment elevation myocardial infarction (STEMI) complicated with heart failure (HF). Methods: A total of 107 patients with HF after acute myocardial infarction were selected for TIMI score. According to the score results, they were divided into low-risk group (0~3 points) with 31 cases, medium-risk group (4~6 points) with 42 cases, and high-risk group (7~14 points) with 34 cases. According to the level of copeptin, they were divided into low copeptin group (60 cases) and high copeptin group (47 cases). The serum copeptin levels and TIMI scores of patients with low, medium and high-risk groups of TIMI and patients with low and high copeptin groups with recurrence/no MACE within 180 days after discharge were compared. Results: The levels of serum copeptin in the low, medium and high-risk groups were (17.59±3.06), (22.76±5.01) and (43.04±11.55) pmol·L-1, respectively. The level of copeptin increased with the increase of TIMI score, and the difference was statistically significant (P<0.05). After 180 days of follow-up, there were 29 cases of major adverse cardiac events (MACE) and 78 cases without MACE. The serum copeptin level in patients with recurrent MACE was significantly higher than that in patients without MACE [ (40.70±12.22) vs (20.13±4.92) pmol·L-1, P<0.05]. The TIMI score of patients with recurrent MACE was significantly higher than that of patients without MACE [ (8±4) vs (5 ±3), P<0.05]. During the 180-day clinical follow-up, the cumulative incidence of cardiac death in the high copeptin group was higher than that in the low copeptin group (P<0.05). Conclusion: Serum copeptin combined with TIMI score has positive clinical reference value for prognosis evaluation of STEMI patients with HF.