Objective: The aim of the study was to investigate predictive factors of the need for persistent antimuscarinic therapy or re-treatment (PR) after discontinuation of antimuscarinic therapy for women with overactive bladder syndrome (OAB). Methods: All consecutive OAB women were enrolled in a prospective cohort study, and treated with solifenacin for 12 weeks in a University Hospital. Factors affecting PR were analyzed by Cox regression analysis. Results: A total of 122 women were enrolled, and 107 women underwent 12-week solifenacin treatment. The dropout rate was 12.3%. The median follow-up period was 20.4 weeks (25-75 interquartile range: 16-102.3 wk). Twenty-seven (25%) women had PR. The median PR-free interval was 125.4 weeks (95% CI = 58.4 to - wk). Nocturia episodes (hazard ratio = 1.54), a suboptimal response (hazard ratio = 2.53), and the strong-desire volume (hazard ratio = 0.992) were independent predictors of PR by Cox backward stepwise regression analysis. The areas under the receiver-operating characteristic curves for nocturia episodes, a suboptimal response, and the strong-desire volume to predict PR were only 0.65, 0.63, and 0.59, respectively. In addition, normalized urinary nerve growth factor level was not significant (hazard ratio = 1.005, P = 0.68) for predicting PR. Furthermore, normalized urodynamic findings did not correlate with PR, a suboptimal response, or changes of Overactive Bladder Symptom Score and urinary nerve growth factor level. Conclusions: Frequent nocturia episodes, a suboptimal response, and small bladder capacity may predict PR after solifenacin treatment. These findings may serve as an initial guide in consultation regarding the treatment of OAB.