© The Authors 2016. Objective The objective of the present study was to examine the relationship of dietary fried fish consumption and risk of cardiovascular events and all-cause mortality. Design Prospective cohort study among participants of the REasons for Geographic And Racial Differences in Stroke (REGARDS) study who resided in the USA. Setting The primary outcome measures included the hazard ratios (HR) of incident CVD including first incident fatal or non-fatal ischaemic stroke or myocardial infarction and all-cause mortality, based on cumulative average fish consumption ascertained at baseline. Subjects Participants (n 16 479) were enrolled between 2003 and 2007, completed the self-administered Block98 FFQ and were free of CVD at baseline. Results There were 700 cardiovascular events over a mean follow-up of 5·1 years. After adjustment for sociodemographic variables, health behaviours and other CVD risk factors, participants eating ≥2 servings fried fish/week (v. <1 serving/month) were at a significantly increased risk of cardiovascular events (HR=1·63; 95 % CI 1·11, 2·40). Intake of non-fried fish was not associated with risk of incident CVD. There was no association found with dietary fried or non-fried fish intake and cardiovascular or all-cause mortality. Conclusions Fried fish intake of two or more servings per week is associated with an increased risk of cardiovascular events. Given the increased intake of fried fish in the stroke belt and among African Americans, these data suggest that dietary fried fish intake may contribute to geographic and racial disparities in CVD.