Methicillin-resistant Staphylococcus aureus (MRSA) infection is known to increase in-hospital mortality, but little is known about its association with long-term health. Two hundred and thirty-seven deaths occurred among 707 patients with MRSA infection at the time of hospitalization and/or nasal colonization followed for almost 4 years after discharge from the Atlanta Veterans Affairs Medical Center, USA. The crude mortality rate in patients with an infection and colonization (23·57/100 person-years) was significantly higher than the rate in patients with only colonization (15·67/100 person-years, P = 0·037). MRSA infection, hospitalization within past 6 months, and histories of cancer or haemodialysis were independent risk factors. Adjusted mortality rates in patients with infection were almost twice as high compared to patients who were only colonized: patients infected and colonized [hazard ratio (HR) 1·93, 95% confidence interval (CI) 1·31–2·84]; patients infected but not colonized (HR 1·96, 95% CI 1·22–3·17). Surviving MRSA infection adversely affects long-term mortality, underscoring the importance of infection control in healthcare settings.