Background: Risperidone is one of the most commonly prescribed antipsychotic medications used to treat several psychiatric disorders. Nevertheless, risperidone’s adverse effects impair patients’ compliance leading to quitting treatment. This study aimed to assess the frequency of risperidone’s adverse effects and investigate the non-genetic factors that may affect adverse effects in Syrian psychiatric patients. Materials and methods: This cross-sectional study included Syrian patients treated with risperidone as antipsychotic monotherapy in Al-Mouwasat University Hospital, Ibn Rushd Psychiatric Hospital, or some private psychiatric clinics in Damascus. Clinical and demographic data were documented. Adverse effects were assessed using Simpson and Angus (SAS) and Udvalg for Kliniske Undersogelser side effect rating scale (UKU). The data analyses were performed using SPSS statistical software, version 26 and GraphPad Prism® software, version 9. Results: Our study encompassed 51 patients treated with risperidone, aged 15 to 58 years with an average of 31.53 ±12.94 years. Males constituted (70.6%), and more than half of the patients were diagnosed with schizophrenia (58.8%). Our findings revealed a high frequency (n=41, 80.4%) of adverse effects, with the extrapyramidal symptoms constituting the majority (58.8%). Four patients discontinued treatment due to the inability to tolerate the adverse effects. fifteen patients (29.4%) used at least one drug that could inhibit risperidone metabolism. The risk of adverse effects increased approximately four times (OR=4.667, 95% CI: 0.7310-54.46, P=0.246) when risperidone was used with CYP2D6 inhibitors with no statistically significant difference. Conclusions: Our study demonstrates a high prevalence of adverse effects associated with Risperidone's use in Syrian psychiatric patients which leads some patients to discontinue treatment. Therefore, careful clinical monitoring is warranted.