Acne is the most common disease of adulthood. Although, no mortality is associated with it, it can result in drastic effects on one’s life if not treated properly. Oral isotretinoin is the most effective treatment of moderate to severe acne. We conducted this study to compare the effectiveness of low doses of isotretinoin with conventional doses in moderate to severe acne. In randomized controlled study 180 patients were enrolled and divided into two groups. Group A received conventional dose of isotretinoin (0.5 mg/kg/day) and group B received low dose of isotretinoin (0.25 mg/kg/day) for 3 months. Patients were fol-lowed up every 4 weeks and at the end of 12 weeks, their improvement was noted and compared. Global acne score was used to assess response and its value less than 19 is taken as a measure of improvement of acne. All 180 patients completed the study. Overall 152 (84.4%) showed effective response and 28 (15.6%) did not improve. Out of those 90 patients who were given conventional therapy 77 (85.6%) improved and 13 (14.4%) did not improve. Among the remaining 90 patients who received low dose isotretinoin 75 (83.3%) showed effective response and 15 (16.7%) did not show effective response. The effectiveness of both groups was compared by applying the chi-square test and shows the p-value was found to be 0.681. Thus no statistically significant difference in the efficacy of both groups is noted. Low dose isotretinoin can opt as a better treatment modality as this regime makes the treatment more acceptable, because of a lower incidence of dose-related side effects, and lower the cost than the conventional dose. © 2020, Colegio de Farmaceuticos de la Provincia de Buenos Aires. All rights reserved.