This systematic review and meta-analysis examined the association between spicy food (chilli pepper, chilli sauce, or chilli oil) consumption with cardiovascular and all-cause mortality. Medline and EMBASE were searched from their inception until February 2020 to identify relevant prospective cohort studies. Hazard ratios (HRs)/relative risk (RRs) were pooled via random-effect meta-analysis. Of the 4387 citations identified, 4 studies (from the United States, China, Italy, and Iran) were included in the meta-analysis. The included studies involved a total of 564 748 adults (aged ≥18 years; 51.2% female) followed over a median duration of 9.7 years. The pooled data suggested that compared with people who did not regularly consume spicy food (none/<1 d/wk), regular consumers of spicy food experienced a 12% (HR/RR_pooled 0.88, 95% CI, 0.86-0.90; I ² = 0%) lower risk of all-cause mortality. Moreover, spicy food consumption was associated with significant reduction in the risk of death from cardiac diseases (HR/RR_pooled 0.82, 0.73-0.91; I ² = 0%), but not from cerebrovascular disorders (HR/RR_pooled 0.79, 0.53-1.17; I ² = 72.2%). In conclusion, available epidemiological studies suggest that the consumption of spicy chilli food is associated with reduced risk of all-cause as well as heart disease–related mortality. Further studies in different populations are needed to confirm this association.