Background: The sex-related impact of metabolic syndrome (MetS) on obstructive coronary artery disease (OCAD) has not been well evaluated. Methods: A total of 1156 patients (62 years and 58% women) with chest pain undergoing invasive coronary angiography (CAG) were recruited from the database of the nation-wide chest pain registry. MetS was defined according to the criteria of the International Diabetes Federation. OCAD was defined as ≥50% stenosis of the left main coronary artery and/or ≥70% stenosis of any other coronary arteries. Results: Women were older than men (65 vs. 59 years, p < 0.001). OCAD (32.0% vs. 30.9%) and MetS (27.8% vs. 27.9%) prevalence rates were similar in both sexes (p > 0.05). The presence of MetS was associated with higher prevalence of OCAD in women (24.5% vs. 47.3%, p < 0.001), but not in men (31.0% vs. 34.3%, p = 0.487). The linear association between the number of components meeting MetS criteria and OCAD prevalence was significant in both sexes (p < 0.001 for each), but it was stronger in women than in men (Chi-square value: 81.9 vs. 14.8, p < 0.001). In a multivariable model, the presence of MetS was independently associated with OCAD in women even after controlling for potential confounders (odds ratio, 1.92; 95% confidence interval, 1.31-2.81; p = 0.001). Conclusions: In patients with chest pain undergoing invasive CAG, the association between the number of components meeting MetS criteria and OCAD prevalence was stronger in women than in men.