Abstract Background and Aims Obesity, a major risk factor for acute coronary syndrome (ACS), is a multifaced disease with different metabolic phenotypes and sex-specific features. We evaluated the long-term cardiovascular risk by different obesity/metabolic phenotypes and by sex in ACS patients. Methods The occurrence of the composite outcome of death, non-fatal re-infarction with or without PCI and/or stroke was evaluated in 674 patients (504 men; 170 women), consecutively hospitalized for ACS and followed-up for 7 years, who were stratified in metabolically healthy (MHNW) and unhealthy normal weight (MUNW), and in metabolically healthy (MHO) and unhealthy obese (MUO) groups, as shown in Figure 1. Results At baseline, 54,6% of patients were included in the MHNW group, 26,4% in the MUNW, 5,9% in the MHO and 13,1% in the MUO, with no sex-differences in the phenotypes distribution. The overall rate of major outcome (100 person-years) in the reference group (MHNW) was higher in men that in women (RR: 1.19 vs 0.6). The Kaplan-Meier curves (see Figure 2) for cumulative survival free from cardiovascular events according to obesity/metabolic status diverged significantly according to sex (long rank test, P= 0.006), being this effect more prominent in men (P=0.011), than in women (P=0.047). Compared to MHNW, the risk increased in obese men (RR: 2.2; 95% CI 1.11-1.54 in MUO group), whereas in women the risk was confined to the metabolically unhealthy subjects (RR: 3.2; 95% CI 1.23-9.98, MUNW group). Conclusions Our data show a sex-specific impact of obesity phenotypes on long-term cardiovascular risk in patients hospitalized for ACS. Thus, while MHO women seemed to be protected over time, in men, obesity had a stronger impact irrespective of metabolic status. These data emphasize the importance of assessing metabolic status and implementing systematic metabolic surveillance in patients undergoing coronary revascularization procedures, even if their weight is normal.