BACKGROUND: An association between infections and vascular events has been observed, but the specific effect of influenza and influenza-like illnesses on triggering acute myocardial infarction (AMI) is unclear. METHODS: Episodes of first AMI from 1 January 2003 through 31 July 2009 were identified using linked anonymized electronic medical records from the Myocardial Ischaemia National Audit Project and the General Practice Research Database. Self-controlled case series analysis was used to investigate AMI risks after consultation for acute respiratory infection. Infections were stratified by influenza virus circulation, diagnostic code, and vaccination status to assess whether influenza was more likely than other infections to trigger AMI. RESULTS: Of 22,024 patients with acute coronary syndrome, 11,208 met the criterion of having had their first AMI at the age of ≥ 40 years, and 3927 had also consulted for acute respiratory infection. AMI risks were significantly raised during days 1-3 after acute respiratory infection (incidence ratio, 4.19 [95% confidence interval, 3.18-5.53], with the effect tapering over time. The effect was greatest in those aged ≥ 80 years (P = .023). Infections occurring when influenza was circulating and those coded as influenza-like illness were associated with consistently higher incidence ratios for AMI (P = .012). CONCLUSIONS: Influenza and other acute respiratory infections can act as a trigger for AMI. This effect may be stronger for influenza than for other infections. CLINICAL TRIALS REGISTRATION: NCT01106196.