Background: Non-adherence to medication in psychiatric patients and identification of related risk factors has provided serious challenges for care service providers. Objectives: The current study aims to determine the psychometrics of a questionnaire used to indicate risk factors related to nonadherence to medication in psychiatric patients. Patients and Methods: Four-hundred patients with psychiatric disorders in Bushehr and Shiraz were enrolled in this cross-sectional study using convenient sampling methods. An initial questionnaire was designed with 23 items. Following the confirmation of content and face validity of the questionnaire, the questionnaire was completed by the participants and 11 experts contributing to the administration. The item impact score, content validity index (CVI), and content validity ratio (CVR) were examined using exploratory factor analysis. In order to calculate the internal and external reliability, the Kuder-Richardson and re-test methods were used. Results: Factor analysis revealed five factors in the questionnaire. Five of 23 items had low content validity and were eliminated. The CVI and CVR of the questionnaire were 0.89 and 0.85, respectively. One statement was eliminated owing to a reduced factor load. Internal reliability was r = 0.86, estimated using the Kuder-Richardson method, and external reliability was r = 0.93, estimated via a Pearson correlation coefficient. Five factors resulting from the questionnaire had optimal reliability according to the Cronbach's alpha coefficient (0.79). Five factors were extracted, including factors related to disease, patient and environment, attitudes toward treatment and therapist, drug side effects, and previous experience to treatment. Conclusions: The questionnaire on risk factors related to medication non-adherence in patients with psychiatric disorders had acceptable psychometric characteristics, and is a useful tool to be implemented in medical centers and psychological clinics.