AIMS: Respiratory infection may be associated with an increased risk of major cardiovascular events. This case-control study describes associations with these events of respiratory infection. METHODS AND RESULTS: The IMS Disease Analyzer Mediplus primary care database was used to identify all cases of first-time diagnosis of myocardial infarction (MI) or stroke and single matched controls. Details were extracted on visits for respiratory infection over the preceding year. A total of 11 155 MI cases and 9208 stroke cases were identified. For MI and stroke respectively, there were 326 and 260 respiratory infections during the month preceding the index date. There was strong evidence of an increased risk of both events in the 7 days following infection, for MI adjusted odds ratio (OR) 2.10 (95% confidence interval 1.38-3.21), for stroke OR 1.92 (95% confidence interval 1.24-2.97). The strength of these associations fell over time. The associations for MI occurred at all levels of initial underlying cardiovascular risk. CONCLUSIONS: There are strong associations between recent respiratory infection and major cardiovascular events, for MI at all levels of underlying risk. The benefits of reducing respiratory infection either through immunization or treating or preventing infection may be substantial.