The use of antipsychotics is associated with an increased risk of obesity. This consideration makes it important to search for determinants that can predict the risk for antipsychotic-induced obesity. In this cross-sectional study, we investigated whether polymorphisms in the HTR2C gene were associated with obesity (body mass index >30 kg/m2) in patients using antipsychotics. We examined polymorphisms in the promoter region of the HTR2C gene ((HTR2C:c.1-142948(GT)n, rs3813928 (-997 G/A), rs3813929 (-759 C/T), rs518147 (-697 G/C)) and an intragenic polymorphism (rs1414334:C>G). The results of the logistic regression were expressed as adjusted odds ratios (OR). In total, we included 127 patients mainly diagnosed with schizophrenia or schizoaffective disorder (89%). The results indicate that a combined genotype carrying the variant HTR2C:c.1-142948(GT)n 13 repeat allele, the common allele rs3813929 C, the variant allele rs518147 C and the variant allele rs1414334 C is significantly related to an increased risk of obesity (OR 3.71 (95% confidence interval: 1.24-11.12)).