Background: depression showed up as potential side effect of isotretinoin in the summary of product characteristics. There have been numerous studies treating this issue yet as a rule not distinguishing any significant depression or suicide risk. Aim of the Work: this study aimedto evaluate the risk of depression in acne patients treated with oral isotretinoin therapy. Methods: one hundred patients with moderate to severe acne were enrolled in non-controlled prospective study. The psychological condition was evaluated at the baseline and fourth month by the Hamilton Depression Rating Scale (HDRS) for all patients. Statistical analysis of HDRS scores was performed. Results: all patients completed the study. Before the treatment 18% of the patients had suffered from mild depressive symptoms. at end of 4 months The patient's scores remained below the subclinical level for depression except only 2 patients one was mildly depressed turned to moderately depressed after four months treatment with isotretinoin other was mildly depressed and still mildly depressed after four months treatment with isotretinoin. The incidence of depression was 1%. Symptoms of depression which occurred in two patients, in which case coexisting situational factors were found to be the cause. Conclusion: our results showed  that the oral isotretinoin treatment for acne at the typical therapeutic dose caused significant reduction in depression scores with a depression incidence only 1%. These changes might be related to clinical effect of isotretinoin. Moreover, the treatment of acne improved symptoms of depression for most patients.