Objective Acute myocardial infarction (AMI) is the leading cause of death and disability globally. There is increasing evidence from observational studies that influenza infection is associated with AMI. In patients with known coronary disease, influenza vaccination is associated with a lower risk of cardiovascular events. However, the effect of influenza vaccination on incident AMI across the entire population is less well established.

Method The purpose of our systematic review of case–control studies is twofold: (1) to estimate the association between influenza infection and AMI and (2) to estimate the association between influenza vaccination and AMI. Cases included those conducted with first-time AMI or any AMI cases. Studies were appraised for quality and meta-analyses using random effects models for the influenza exposures of infection, and vaccination were conducted.

Results 16 studies (8 on influenza vaccination, 10 on influenza infection and AMI) met the eligibility criteria, and were included in the review and meta-analysis. Recent influenza infection, influenza-like illness or respiratory tract infection was significantly more likely in AMI cases, with a pooled OR 2.01 (95% CI 1.47 to 2.76). Influenza vaccination was significantly associated with AMI, with a pooled OR of 0.71 (95% CI 0.56 to 0.91), equating to an estimated vaccine effectiveness of 29% (95% CI 9% to 44%) against AMI.

Conclusions Our meta-analysis of case–control studies found a significant association between recent respiratory infection and AMI. The estimated vaccine effectiveness against AMI was comparable with the efficacy of currently accepted therapies for secondary prevention of AMI from clinical trial data. A large-scale randomised controlled trial is needed to provide robust evidence of the protective effect of influenza vaccination on AMI, including as primary prevention.