Abstract Background: Acne vulgaris is chronic inflamatory disease of the pilosebaceous unit.Patients experience psychological burdens like depression ,anxiety, and low self- esteem. Isotretinoin is used in the treatment of severe and recalcitrant acne; however, this treatment is associated with a number of partialy common adverse effects that it sometimes may stop the process of treatment. The aim of this study is to evaluate the effect of oral omega 3 on side-effects of isotretinoin . Materials and Methods: One hundred eighteen patients with severe acne vulgaris were randomly divided into two groups. Control group received isotretinoin (0.5 mg∕kg) alone and case group received isotretinoin (0.5 mg∕kg) combined with omega 3 (2 capsuls) daily. The duration of treatment was 16 weeks.Mucocutaneous side-effects were assessed in patients(4, 8, 12, 16th wk). Results: Lip dryness (4, 8, 12th wk) and dryness of nose, skin, eye in the 4 th week in the patients with acne vulgaris treated with isotretinoin and omega3 was lesser than in the patients treated with isotretinoin alone, that this difference was statistically significant (p<0.001). Conclusion: Based on the results of this study, Omega 3 decreased the mucocutaneous side effects in the patients with acne vulgaris who received isotretinoin.