AbstractEvidence from literature supports the existence of associations between serotonin-related genetic variants and obsessive-compulsive disorder (OCD), but few studies have explored the involvement of serotonin receptor type 3 genes (HTR3) in OCD. To identify whetherHTR3variability affects an individual’s susceptibility to OCD, we examined 10HTR3variants in 596 individuals with OCD and 599 controls. A significant difference existed in the genotypic distribution of theHTR3Bvariant rs1176744 between individuals with OCD and controls (odds ratio [OR] = 0.74, 95% confidence interval [CI] = 0.60–0.91,P = 0.0043). A protective haplotype inHTR3Bwas also associated with OCD (OR = 0.77, CI = 0.63–0.95, permutatedP = 0.0179). Analyses of OCD sub-phenotypes demonstrated significant associations between rs3758987 and early onset OCD in male subjects (OR = 0.49, CI = 0.31–0.79,P = 0.0031) and among rs6766410, rs6443930, and the cleaning dimension in female subjects (OR = 0.36, CI = 0.18–0.69,P = 0.0016 and OR = 0.47, CI = 0.29–0.79,P = 0.0030, respectively). Additionally, rs6766410 was related to contamination-based disgust in OCD (P = 0.0044). These results support that commonHTR3variants are involved in OCD and some of its clinical phenotypes.