Objective: To assess health-related quality of life and associated factors in patients treated with atypical antipsychotics, as well as to determine utility values using the EuroQol-5D-3L instrument. Methods: A cross-sectional study was conducted at a state-run pharmacy in the Brazilian National Health System. Individuals were included if they were using a single atypical antipsychotic and completed the EuroQol-5D-3L. Sociodemographic, behavioral, and clinical data were collected. The dependent variable was the EuroQol-5D-3L utility score. Associations between the independent variables and the dependent variable were analyzed in a multiple linear regression model. Results: A total of 394 patients were included, and their mean utility score was 0.664±0.232. Patients treated with clozapine had the highest mean score (0.762 [0.202]), followed by olanzapine (0.687 [0.230]), risperidone (0.630 [0.252]), ziprasidone (0.622 [0.234]), and quetiapine (0.620 [0.243]). The following variables were related to higher utility scores: income, employment, clozapine use, no illicit psychoactive substance use, no suicide attempts, and no comorbidities. Conclusion: Evaluating health-related quality of life differences in the available atypical antipsychotics can facilitate the choice of treatment, improve health outcomes, and ensure rational prescriptions.