OBJECTIVE Several polymorphisms have been reported in the 5-HTTLPR of the serotonin transporter gene (SLC6A4). Family-based evidences for the association of 5-HTTLPR polymorphisms with OCD were previously reported but results were controversial. The present study investigated the possible correlation of SLC6A4 polymorphisms (5-HTTLPR, rs25532, rs25531) in Iranian OCD patients considering gender, age of onset, family history of psychiatric disorders, obsessive and compulsive subtypes and severities. METHODS The included OCD patients fulfilled the criteria for DSM-IV-TR whom Y-BOCS score was more than 9. Blood samples (184 cases and 192 controls) were genotyped by means of PCR-RFLP. RESULTS Mean of Y-BOCS scores of included patients was 20.1 ± 0.69. Rs25532 CC genotype showed significant association with OCD in men and were detected more in the patients reported positive family history of psychiatric disorders but the other single loci (5-HTTLPR and rs25531) did not associate with OCD. Haplotype analysis showed significant association of 14-A variant with OCD and revealed the association of 14-A/14-A genotype with familial form of OCD. CONCLUSIONS The findings of this study showed the association of SLC6A4 variants with familial form of OCD and proposed stratified analyses in the genetic studies facilitate identification of genetic risk factors for this heterogeneous disorder.