OBJECTIVES: Benign prostatic hyperplasia (BPH) is a highly prevalent condition, affecting more than 50% of men aged > 60 years. Alpha1-adrenergic blockers (ABs) tamsulosin, alfuzosin, doxazosin, and terazosin are commonly used pharmacologic treatments for benign prostatic hyperplasia (BPH). However, there are limited data on intra-class comparisons of ABs with respect to treatment failure, particularly in the U.S. This study aimed to assess the rate of treatment failure with tamsulosin versus other ABs among patients with BPH in a U.S. setting. METHODS: A retrospective database analysis was performed using health-care claims for patients with an ICD-9 diagnosis for BPH between 1Q2000 and 3Q2005. Only patients, aged > 35 years, newly initiated with AB therapy were included; those with a history of prostate or urogenital disease were excluded. Treatment failure was defined as switching to another AB therapy or undergoing BPH-related surgery. Time-to-treatment failure was assessed using Kaplan-Meier survival analyses; Cox proportional hazard regression models were used to control for differences in baseline characteristics. Alfuzosin, introduced in 2004, was evaluated in an exploratory analysis with a shorter, 15-month follow-up period. RESULTS: At baseline, patients receiving tamsulosin (n=10,340) were younger and more likely to see urologists than those receiving doxazosin (n=3,088) or terazosin (n=2,710) (p<0.050 for all). Rates of treatment failure were lower for patients receiving tamsulosin compared to those receiving doxazosin and terazosin in the Kaplan-Meier analysis (p<0.001 for both); multivariate Cox regression models confirmed these findings versus doxazosin (HR = 1.8, p<0.001) and terazosin (HR = 2.1, p<0.001). Compared to tamsulosin, patients receiving alfuzosin (n=608) were also at greater risk of treatment failure (HR = 2.6, p<0.001). CONCLUSION: Among the study population, initial treatment with tamsulosin resulted in reduced rate of treatment failure compared to doxazosin and terazosin. Definitive conclusions for alfuzosin require studies with longer follow-up periods.