Background Sex differences in acute coronary syndrome (ACS) have been well studied in major registries and clinical trials in Western populations. Limited studies have examined the sex differences in ACS using a large number of Asian women as the subjects. Objectives The aim was to study the sex differences in ACS using the NCVD-ACS (National Cardiovascular Disease Database?Acute Coronary Syndrome) registry. Methods We analyzed 13,591 ACS patients, of which 75.8 were men and 24.2 were women, from March 2006 to February 2010. Data were collected on demographic characteristics, risk factors, anthropometrics, treatments, procedures, mortalities, and complications. The results were compared among 3 cohorts of ACS (ST-segment elevation myocardial infarction [STEMI], non?STEMI, and unstable angina). Results Women were older and more likely to have diabetes, hypertension, previous heart failure, and cerebral vascular accidents than men were. Women were less likely to receive in-hospital administration of aspirin, beta-blockers, angiotensin-converting enzyme inhibitors, or angiotensin receptor blockers, and they were less likely to undergo angiography and percutaneous coronary intervention. In STEMI, a significantly lower proportion of women than men received primary percutaneous coronary intervention (6.2 vs. 6.7 , respectively, p = 0.000) and fibrinolysis (64.4 vs. 74.6 , respectively, p = 0.000). In addition, with regard to STEMI, women had a significantly higher unadjusted in-hospital mortality rate than men did (15.0 vs. 8.1 , respectively, p <0.000). There was no statistically significant in-hospital mortality difference between sexes for non-STEMI and unstable angina. After adjustment for age and other covariates, a multivariate analysis showed no sex differences in the in-hospital mortality in all spectrums of ACS. Conclusions Our study showed significant sex differences in the demographic characteristics, risk factors, treatments, and outcomes of ACS. More importantly, in ACS patients, we found evidence of suboptimal treatments and interventions in women versus men. Our findings provide an opportunity to narrow the sex gap in the care of women with ACS in Malaysia.