Although several studies have tested the association between bipolar disorder (BD) and the Val108 (H, high-activity allele)/158Met (L, low-activity allele) polymorphism of the catechol-O-methyltransferase (COMT) gene, most of the results showed no significant association. However, an association between the H or L allele and bipolar disorder (BD), particularly, between L allele and rapid-cycling form has been reported; it has also been suggested that the variation in the COMT gene modifies the course of BD and there is a tendency for the L allele amongst the female patients. In this study, the researchers aimed to evaluate the association between BD and COMT gene H/L polymorphism considering the influence of gender in a group of Turkish patients.One hundred and thirty-five BD patients (71 male and 64 female) and 171 controls were included. Polymerase chain reaction-based endonuclease digestion method was used.Genotypic distribution in patients and controls were in Hardy–Weinberg equilibrium. No significant difference was found in genotypic and allelic frequencies between patients and controls. However, female patients had H allele more frequently than male patients and female healthy controls. Females had more depressive and less manic episodes than males. Number of total episodes was associated with H allele in all patients.Distribution of COMT genetic polymorphism was not significantly different between the patients and controls. However, it has been found an association of H allele with female patients and number of episodes among all patients.