OBJECTIVE: This study evaluates the real world persistency of therapy for overactive bladder (OAB), comparing tolterodine, oxybutynin and flavoxate head-to-head in a large sample extracted from a U.S. drug claim database. Clinical trials have shown tolterodine has equal efficacy to oxybutynin in reduction of OAB symptoms and a significantly better side-effect profile. METHOD: A longitudinal study was conducted using drug claims from PCS Health Systems. The study cohort consists of 4602 “naïve tolterodine users”, 7291 “naïve oxybutynin users” and 2127 “naive flavoxate users.” Survival analysis was used to estimate the “persistence rate”—defined as the proportion of patients who are still on a drug treatment during or after a defined period of continuous treatment for the drug. A Cox-regression model was used to assess the net effect of using tolterodine or oxybutynin on the persistence of drug therapy controlling for differences in the patients’ demographics, comorbid conditions, and other factors. RESULTS: The persistence on tolterodine was 30% higher than that on oxybutynin on continuous treatment periods of 31-60 days, and 90% higher for 301-360 days of therapy. The persistence on tolterodine was 430% higher than that on flavoxate for treatment periods of 30-60 days and 340% higher for 301-360 days of therapy. The average length of continuous treatment for naive tolterodine users was the longest of the three drugs: 143(3.9) days compared to 91(2.6) days for oxybutynin and 41(4.6) days for flavoxate. The adjusted odds-ratio of terminating drug treatment for tolterodine vs. oxybutynin users was 0.66 (p>0.001). CONCLUSIONS: Patients using tolterodine were significantly more likely to continue their treatment than those choosing other OAB drugs. The better persistence for tolterodine users should result in longer symptom relief for patients, particularly for those who are in need of long-term treatment but are distressed by side effects.