Oral isotretinoin is effective for acne vulgaris but concerns remain regarding its adverse effects. This study aims to evaluate the safety and efficacy of isotretinoin for acne vulgaris in Asian patients. We conducted a 4-year retrospective study on all patients with acne vulgaris treated with isotretinoin, between January 2005 and December 2008 at the National Skin Centre in Singapore. Medical records were reviewed for information on patient demographics, acne severity, isotretinoin dose, duration, adverse effects and outcome. There were 2,255 patients, with a mean age of 22.5 years, male:female ratio of 2.5:1 and 82.3% being Chinese. The mean starting dose of isotretinoin was 0.4 mg/kg and on average, patients received 7.8 months of treatment at a mean dose of 0.5 mg/kg. Mean total cumulative dose was 95.6 mg/kg. Vast majority (93.9%) achieved complete remission or substantial improvement. Thirty-eight (2.2%) and 24 patients (2.7%) developed elevated serum levels of alanine and aspartate aminotransferases subsequent to treatment. There were 194 (12.1%) and 80 (4.8%) patients who developed hyperlipidaemia and hypertriglyceridaemia respectively. Isotretinoin was generally well-tolerated, with 6.4% (n = 145) discontinuing due to side-effects. This study reaffirms the overall safety and efficacy of oral isotretinoin in Asian patients with acne vulgaris.