Neurogenic dysfunction of the lower urinary tract is one of the challenging diseases with high burdens in urology. Our study aims to evaluate the efficacy of a 4-week treatment with Solifenacin and Trospium chloride and assess their safety and impact on quality of life. Following the selection of 206 stroke patients from two centers who met specific eligibility criteria, including a clinical diagnosis of stroke, normal cognitive function, and the presence of lower urinary tract symptoms (LUTS), participants were randomly assigned to receive oral Solifenacin, Trospium chloride, or a placebo. Under the supervision of the Ethics Committee, the baseline characteristics, compliance with medication, and outcomes were monitored, gathered, and analyzed. The majority of participants were male, with a mean age of 67.3, and most had ischemic stroke. The groups had no significant difference in urinary symptoms after stroke. All of the symptoms in the study groups, according to the NBSS questionnaire, were decreased following treatment compared to the baseline (p < 0.05). After treatment, ICIQ-OAB, and ICIQ-LUTS-QOL total scores and bothersome scores decreased significantly compared to baseline (p < 0.001). When compared to the placebo, both Trospium chloride and Solifenacin alleviated symptoms according to the NBSS questionnaire and ICIQ-LUTS-QOL, total ICIQ-OAB, and the total score of ICIQ-OAB-Bothersome. However, the total LUTS-QOL-Bothersome score did not change in the active treatment groups compared to the placebo. While comparing the two drugs, these values were similar except for the total score of LUTS-QOL-Bothersome, ICIQ-OAB, and ICIQ-OAB-Bothersome in favor of the Solifenacin group. Moreover, Solifenacin had fewer side effects compared to Trospium chloride or placebo. The study analyzed 206 stroke patients in two international centers and found both drug arms effective in treating overactive bladder. However, inconsistencies were found in efficacy and safety, necessitating further studies with larger populations. This triple-blind, multicenter, randomized controlled trial was done on 206 stroke patients after getting Ethical Committee approval and registering the project on IRCT (IRCT20160606028304N2).