Background: There is a concern about geographical region heterogeneity regarding clinical benefit of β-blocker (BB) therapy in heart failure with reduced ejection fraction (HFrEF). This study sought to compare benefits of BB use within randomized controlled trials (RCTs) that enrolled patients with HFrEF from North America (NA) compared with other regions of the world (ROW)., Methods: We conducted a meta-analysis using MEDLINE, EMBASE, Cochrane Library, Web of Science, and Scopus (inceptions-December 2012) of BB RCTs stratified according to NA vs ROW. The primary end point was all-cause mortality and secondary end points were cardiovascular death, sudden death, death due to pump failure, and premature drug discontinuation. Summary odds ratios (ORs) and 95% confidence intervals (CIs) for each outcome were calculated with interaction terms for region. Two-sided P values were calculated with P < 0.05 considered significant., Results: The analysis included 16 RCTs with 14,452 patients; 7 trials were conducted in NA and 9 trials in ROW with follow-up durations of 3-58 months. All-cause mortality was consistently reduced in NA (OR, 0.82; 95% CI, 0.71-0.96; P = 0.01) and ROW (OR, 0.76; 95% CI, 0.69-0.84; P < 0.001; P-interaction = 0.40). Overall and according to region, all secondary end points including premature drug discontinuation were also less with BB therapy (P-interactions all ≥ 0.10)., Conclusions: For the regions represented in the included trials, there is no evidence to suggest that geographic region is a significant moderator of clinical outcomes with BB therapy in HFrEF patients., (Copyright © 2014 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)