The purpose of this study was to compare the efficacy of the cognitive-behavior therapy (CBT), exposure and response prevention (ERP) and Fluoxetine in the obsessive-compulsive patients. The experimental design was selected and 59 patients with obsessive-compulsive disorder (OCD) diagnosis were randomly assigned to 4 groups: cognitive-behavioral therapy ,exposure and response prevention ,Fluoxetine and waiting-list. Patients in the four groups were seleted with respect to the variables such as age, sex, academic and marital status. For gathering data Moudsley Obsessive-Compulsive Inventory (MOCI), Beck Depression Inventory-II (BDI-II), Beck Anxiety Inventory (BAI) were used as instruments. The patients of the four groups completed these three questionnaires in 3 stages (pre test ,post test ,follow-up with 2 months interval). The data were analysed by multivariate analyses of Anova (MANOVA-1 way) ,and post hoc test (T tukey). The findings indicated the treatment effect of CBT on OCD severity was more significant than Fluoxetine in short-term and long-term (P<0.05، P<0.01, respectively). This difference between CBT and waiting-list groups was also significant (P<0.01). The efficacy of ERP on OCD severity was more than Fluoxetine only in short-term (P<0.05). This difference between ERP and waiting-list groups was significant in both short-term and long-term too (P<0.01). Moreover ,This difference between Fluoxetine and waiting-list groups was significant only in short-term (P<0.05). On the efficacy of fluoxetine in depression severity in both short-term and long-term was more significant than CBT (P<0.01) and ERP (short-term P<0.01, long-term P<0.05). In addition ,this difference between ERP and waiting-list groups was significant in both short-term and long-term (P<0.01, P<0.05, respectively). On the basis of both findings it can be concluded that CBT ,ERP and fluoxetine are effective on OC and depressive symptoms of OCD patients but the long-term efficacy of CBT and ERP is higher than fluoxetine.