Background Previous studies have reported the beneficial effects of spice consumption on lipid profiles, fasting glucose, and blood pressure, which suggests that spice consumption could affect the risk of cardiovascular disease, diabetes mellitus, and consequently mortality. The objective of this study was to evaluate the relationship between consumption of turmeric, black or chili pepper, cinnamon, and saffron with overall and cause‐specific mortality in an adult population in Iran. Methods and Results We used data from the Golestan Cohort Study, which has followed 50 045 participants aged 40 to 75 years from baseline (2004–2008). After establishing the exclusion criteria, 44 398 participants were included in the analyses. Spice consumption data were extracted from the baseline Food Frequency Questionnaire. Cox models were used to estimate hazard ratios ( HR ) and 95% CI for overall and cause‐specific mortality, comparing the ever consumers to the never consumers as a reference group for each type of spice (adjusted for known and suspected confounders). During 11 years of follow‐up, 5121 people died. Turmeric consumption was associated with significantly reduced risk of overall mortality ( HR =0.90, 95% CI =0.85–0.96) and cardiovascular mortality ( HR =0.91, 95% CI =0.82–0.99). Black or chili pepper consumption was associated with significantly reduced risk of overall mortality ( HR =0.91, 95% CI =0.86–0.98). Saffron consumption was associated with significantly reduced risk of overall ( HR =0.85, 95% CI =0.77–0.94) and cardiovascular mortality ( HR =0.79, 95% CI =0.68–0.92). We found no associations with cinnamon consumption or between any of these spices and cancer mortality. Conclusions Consuming turmeric or saffron was associated with decreased risk of overall and cardiovascular mortality. The hypothesis of a protective effect of spice consumption on mortality should be tested in other prospective studies.