Background/Objective: Dietary recommendations for the consumption of spicy foods in uninvestigated heartburn are still under debate. We examine the association between spicy food consumption and the prevalence of uninvestigated heartburn in a large sample of Iranian adults. Methods: This cross-sectional study was conducted among 4,633 Iranian adults living in Isfahan (2,046 men, 2,587 women) in 2010. The average daily intake of spicy foods was estimated using a dietary habit questionnaire. Uninvestigated heartburn was defined, using a validated Rome III questionnaire, as the presence of heartburn sometimes, often or always during the last 3 months. Results: Uninvestigated heartburn was prevalent in 23.8% (n = 1,103) of participants. After controlling for potential confounders, including dietary behaviors and body mass index, men consuming spicy foods ≥10 times/week were 2.63 times more likely to have uninvestigated heartburn (95% CI: 1.28-5.36) compared with those who never consumed spicy foods. Also, those men with the highest consumption of spicy foods were 3 times more likely to experience heartburn frequently (95% CI 1.44-6.39) compared with men with the lowest intake. No overall significant associations were found between the consumption of spicy foods and uninvestigated heartburn, including the frequency and severity of heartburn, in women. When the analysis was restricted to those with uninvestigated heartburn, no significant associations were found between consumption of spicy foods and frequency of heartburn either in men or women. Conclusion: The present findings suggest that high consumption of spicy foods was associated with a greater risk of uninvestigated heartburn in men, but not in women. Further studies, particularly of a prospective nature, are needed to confirm our findings, as well as underlying mechanisms.