Objective Gender differences in the clinical presentation and management of patients with acute coronary syndrome (ACS) have been reported in different parts of the world with contradicting results. We aimed at investigating the presence of gender bias in patients admitted with ACS to Aseer Central Hospital (ACH). Methods A retrospective cohort of all consecutive patients admitted to ACH with the diagnosis of ACS, during the period between the 1st of June 2007 and the 31st of May 2009 was studied. Data on demographic and clinical profiles, management and outcomes of ACS patients were collected and compared for both genders. Results The present study included 148 females and 397 males. Females were significantly older than males (62.9 ± 14.2 vs. 60 ± 13.4, respectively, P < 0.03), were less likely ever to have smoked (0.7% vs. 26.2%, respectively, P < 0.001), less likely to have had a history of hyperlipidemia (10.8% vs. 22.2%, respectively, P < 0.003) or family history of ischemic heart disease (10.1% vs. 18.9%, respectively, P < 0.014). Female patients presented more with atypical presentation (42.6% vs. 28.9%, respectively, P < 0.003), more with unstable angina (72.3% vs. 50.4%, respectively, P < 0.001), and less with ST-elevation myocardial infarction (18.9% vs. 40.8%, respectively, P < 0.001). Furthermore, they had significantly lower levels of hemoglobin compared to males (12.9 ± 2.3 vs. 14.5 ± 2.2 g/L, respectively, P < 0.001), and higher levels of high density lipoprotein (1.1 ± 0.4 vs. 0.98 ± 0.4 mmol/L, respectively, P < 0.008). Left ventricular ejection fraction was significantly higher in female patients compared to males (50.9 ± 14 vs. 45.8 ± 14, respectively, P < 0.003). Coronary angiography showed a higher rate of normal findings (29.3% vs. 8.9%, respectively, P < 0.001) and less severe disease (46.7% vs. 60.3%, respectively, P < 0.027) in women, however, they were less likely to undergo invasive revascularization procedures (31% vs. 42.8%, respectively, P < 0.013). No significant differences were found between both sexes regarding in-hospital mortality or re-infarction rates. Conclusion We documented gender differences in both clinical presentation as well as management of patients admitted with ACS to ACH. However, there were no significant differences between both genders regarding the clinical in-hospital outcomes. Emphasis should be made to avoid such bias in the future.