Abstract Background To assess treatment persistence and adherence in men ≥45 years of age with lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH), using prescription records from the Netherlands IMS Lifelink™ LRx database. Methods In this retrospective, observational cohort study, we identified men who received combination therapy with an α-blocker plus an antimuscarinic (e.g. solifenacin or tolterodine) between 1 November 2013 and 31 October 2014. Treatment could be received as a fixed-dose combination (FDC) tablet or as two drugs administered together (concomitant therapy), if both combination drugs were prescribed within 30 days. The primary objective was to assess treatment persistence, defined as the time from initiation of combination therapy until first discontinuation of the FDC or at least one of the drugs given concomitantly (i.e. ≥30 days without prescription renewal). Subgroup and sensitivity analyses were conducted to assess persistence by antimuscarinic agent, and with different gap lengths used to define discontinuation (45, 60 and 90 days), respectively. Results A total of 1891 men received an α-blocker plus an antimuscarinic (FDC, N = 665; concomitant therapy, N = 1226). Median time to discontinuation was significantly longer with FDC versus concomitant therapy (414 vs. 112 days; adjusted hazard ratio [HR] 2.04, 95% confidence interval 1.77, 2.35; p < 0.0001). Persistence at 12 months (51.3% vs. 29.9%) was also significantly greater with FDC compared with concomitant therapy. Assessment of antimuscarinic subgroups showed that median time to discontinuation was longest with solifenacin combinations (214 days) compared with other antimuscarinic combinations (range, 47–164 days; adjusted HR range, 1.27–1.77, p = 0.037). No observable impact on treatment persistence was found by adjusting the gaps used to define discontinuation. Discussion This study of real-world evidence of men with LUTS/BPH treated with α-blocker plus antimuscarinic combination therapy in ...