Sex differences in coronary artery disease presentation and outcomes have been described. The aim of this study was to compare sex disparities in chronic total occlusion (CTO) management and long-term outcomes. All consecutive patients with at least one CTO diagnosed in our center between 2010 and 2014 were included. Demographic and clinical data were registered. All-cause and cardiac mortality were assessed during a median follow-up of 4.03 years (IQR 2.6–4.8). A total of 1248 patients (67.3 ± 10.9 years; 16% female) were identified. Women were older, had a higher prevalence of type 2 DM and a lower ventricle ejection fraction compared to men (p < .05). Although women had major proportion of positive result for severe ischemia-viability test (86% vs. 74%; p = .01), they were more often treated with MT alone compared to male (57% vs 51%; p = .02). During follow-up, 386 patients (31%) died. Women presented a higher rate of all-cause and cardiac mortality, and hospitalizations for heart failure independently of treatment strategy, compared to men (p < .001). In multivariable analysis female sex was associated with higher cardiac mortality HR 1.67, 95% CI 1.10–2.57; p < .001. Among women, the independent predictors for all-cause and cardiac mortalities were age, MT of the CTO and ACEF (age, creatinin and ejection fraction) score. A significant sex gap regarding CTO treatment was observed. Female sex was an independent predictor for cardiac mortality at long-term follow-up. More data are needed to support these findings. •Despite recent advancements in CTO treatments, a significant sex gap remains.•Women were more often treated with MT alone, but men were more likely to undergo invasive strategies.•Female sex in CTO patients was associated with higher cardiac mortality.