The association between intakes of riboflavin and mortality has not been examined intensively in general populations. In this study, 10,480 adults in the 2005-2016 National Health and Nutrition Examination Survey (NHANES) were followed-up until 2019 for their vital status. Riboflavin and folate were assessed by two-day 24 h recall. The date and cause of death were obtained from the US Mortality Registry. The risks of all-cause mortality and cardiovascular disease (CVD) mortality were investigated using a Cox regression analysis. During a mean of 8.5 years follow-up, there were 1214 deaths registered (including 373 deaths from CVD and 302 from cancer). Compared to low level (quartile 1, Q1) of riboflavin intake, the hazard ratios (HRs) (95% confidence interval (CI)) for high level (quartile 4, Q4) were 0.53 (0.31-0.90) for CVD mortality and 0.62 (0.48-0.81) for all-cause mortality. The inverse association between riboflavin intake and CVD mortality was only significant among those with a high intake of folate ( p for interaction 0.045). Those with a high folate intake (Q4) and low intake of riboflavin (Q1) had the highest risk of CVD mortality (HR 4.38, 95% CI 1.79-10.72), as compared with a high intake of both riboflavin and folate. In conclusion, riboflavin intake was inversely associated with all-cause mortality and CVD mortality, and the association was modified by folate intake.