Background: Although coffee consumption is increasing rapidly, the results of previous studies regarding the association between coffee consumption and stroke risk have been conflicting. This was a multi-center cross-sectional study that aimed to evaluate the relationship between coffee consumption and stroke risk in Korean population. Methods: Data were obtained from the Health Examinees (HEXA) Study, which involved 146,830 individuals aged 40-69 years. Coffee consumption was categorized as none, < 1 cup/day, 1 to < 3 cups/day, and ≥ 3 cups/day. We used logistic regression models to examine the association between coffee consumption and the risk of stroke while controlling for potential confounders and performed subgroup analyses. Results: After adjusting for age and various possible confounders, high coffee consumption was associated with a 38% lower odds ratio for stroke in women (none vs. ≥ 3 cups/day: OR, 0.62; 95% CI 0.47-0.81; P for trend < 0.0001). No significant association was found in men (none vs. ≥ 3 cups/day: OR, 0.84; 95% CI, 0.66-1.07; P for trend = 0.1515). In analyses stratified by covariates, an inverse association between coffee consumption and stroke risk was most evident among healthy women who were younger, non-obese, non-hypertensive, non-diabetic, non-smokers, and non-alcohol drinkers. Conclusion: Our results suggest that higher coffee consumption may have protective benefits with regards to stroke risk in middle-aged Korean women.