We sought to investigate the prevalence of left main coronary artery significant stenosis (LMSS) (≥50% of the luminal diameter) in an angiographic series of patients, to describe the associated coronary stenoses, and to assess the influence of age and gender on these findings. The angiograms of 17,323 consecutive patients from January 1, 1984 to December 31, 2003 were retrospectively analyzed. LMSS was found in 823 patients (4.8%) and was more predominant in men (p <0.001). Men with LMSS (median age 63 years, interquartile range 57 to 69) were younger than the women (median age 67 years, interquartile range 61 to 72, p <0.001). Logistic regression analyses revealed male gender (odds ratio [OR] 1.79, 95% confidence interval [CI] 1.46 to 2.18, p <0.001) and age (OR 1.05, 95% CI 1.04 to 1.06, p <0.001) as independent predictors of LMSS. In the total series, luminal narrowing ≥50% in the right coronary artery, the left circumflex artery, the left anterior descending artery, the intermediate artery, first and second obtuse marginal branch, posterior descending artery, and posterolateral branch was significantly more frequent in association with LMSS. Approximately half of the patients with LMSS also had triple-vessel disease. Co-existent disease in 3 major vessels with minor branches was more evident in men (men/women OR 1.77, 95% CI 1.08 to 2.88, p = 0.02). In contrast, the remaining 4.7% of patients with LMSS, and this was more frequent in women (men/women OR 0.31, 95% CI 0.15 to 0.61, p = 0.001). In conclusion, men presented more frequently with LMSS and at a younger age than women. Also, LMSS with co-existent triple-vessel disease was more common in men.