Background: There is substantial epidemiological evidence demonstrating that influenza contributes to cardiovascular events in patients who already have cardiovascular diseases. However, it is unclear the extent to which influenza vaccination influences the prognosis of patients with ischemic heart disease (IHD)., Methods: We conducted a search for eligible randomized controlled trials (RCTs) in PubMed, Cochrane, and Embase on March 11, 2024, to investigate the effect of the influenza vaccine on the prognosis of patients with IHD. The effect sizes were combined using random-effects models, and the Trial Sequential Analysis (TSA) was used to assess the reliability and validity of the results., Results: Five RCTs with a total of 5,659 patients with IHD were included. Use of influenza vaccine reduced the risk of major cardiovascular events (risk ratio [RR]=0.67, 95% confidence interval [CI] 0.52-0.87, number-needed-to-treat [NNT] of 37, high certainty), cardiovascular death (RR=0.55, 95%CI 0.35-0.87, moderate certainty), all-cause mortality (RR=0.58, 95%CI 0.40-0.84, high certainty) and myocardial infarction (MI) (RR=0.66, 95%CI 0.46-0.93, high certainty) in patients with IHD compared with control. The analysis revealed no significant benefit regarding hospitalization for heart failure (HF) (RR=0.91, 95%CI 0.21-3.99, moderate certainty) and revascularization (RR=0.59, 95%CI 0.10-3.45, moderate certainty). The NNT to avoid 1 event was 37 for major adverse cardiovascular events (MACE), 56 for cardiovascular death, 67 for MI, 41 for all-cause death. TSA showed that the benefit of influenza vaccine in reducing MACE was conclusive., Conclusion: These studies suggested that the use of influenza vaccine may reduce the risk of MACE in patients with IHD., Competing Interests: Declaration of Competing Interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024. Published by Elsevier Ltd.)