Background Some studies have shown that statins reduce the efficacy of influenza vaccine. The aim was to examine the impact of statins on influenza and influenza vaccine effectiveness (VE). Methods This study was a post-hoc analysis of subjects in a prospective case-control study of influenza and acute myocardial infarction, where data on influenza infection, vaccination and statin use was collected. Study participants, aged ≥40 years were recruited from tertiary hospitals in Sydney from 2008 to 2010. Univariate and logistic regression analysis was performed. Results Of total 559 participants, 276 (49.4%) had been vaccinated and 196 (35.1%) were taking statins. The rate of laboratory confirmed influenza was significantly higher in unvaccinated statin users (adjusted odds ratio (AOR), 2.44; 95% CI: 1.06-5.62) compared to unvaccinated non-users. The VE was 98% overall, and not significantly different between statin users (92.4%) and non-statin users (100%). In adjusted analysis of all subjects, vaccination was significantly protective (AOR, 0.02; 95% CI: 0.01-0.15), and statins remained significantly associated with influenza risk (AOR, 2.47; 95% CI: 1.08-5.64). Conclusion No significant difference in influenza VE by statin use, and vaccine was highly effective in both statin users and non-users. There was a significantly higher risk of influenza among statin users, independent of vaccination. Statins may increase the risk of influenza through immunomodulatory mechanisms, or this may be confounded by other risk factors for influenza. It is important that people on statins should be vaccinated against influenza.