Uterine leiomyoma (ULM) is the most common gynecological benign tumor that is affecting around 20-50 % of women over the age of 30. Although its molecular pathogenesis is still unknown, ULM has a multifactorial etiology determined by both genetics and environmental factors. The present study was designed to find out whether Val158Met polymorphism in the catechol-o-methyltransferase (COMT) gene is associated with the risk of ULM. We analyzed COMT Val158Met polymorphism in 105 ULMs patients and 105 healthy subjects using a polymerase chain reaction-based restriction fragment length polymorphism assay. We found remarkably similar frequencies in ULM compared with controls for COMT Val158Met genotypes and alleles, and no association was found between ULM and this polymorphism (p = 0.46). The COMT 158 Met allele in patients with large (≥5 cm) fibroids was higher than in patients with small (<5 cm) fibroids, and significant association was found between fibroid size and COMT 158 Met allele (p = 0.011, OR 0.50, 95 %CI 0.28-0.90). Our results reflect that COMT Val158Met polymorphism is not associated with an increased risk of ULMs, but Val158Met polymorphism may be a risk factor for development of large fibroids in Turkish patients with ULM.