OBJECTIVE Postbariatric hypoglycemia affects >50% of individuals who have undergone Roux-en-Y gastric bypass surgery. Despite the often debilitating nature of this complication, existing treatment options are limited and often inefficient. Dasiglucagon is a stable gluca-gon analog available in a ready-to-use formulation and was recently shown to mitigate postbariatric hypoglycemia in experimental settings. Here, we aimed to evaluate the hypoglycemic hindering potential of dasiglucagon in an outpatient trial. RESEARCH DESIGN AND METHODS We conducted a randomized, double-blind, placebo-controlled, crossover, proof-of-concept study at the Center for Clinical Metabolic Research at Gentofte Hospital in Denmark. The study included 24 individuals who had undergone Roux-en-Y gastric bypass surgery (n = 23 women) with continuous glucose monitor–verified postbariatric hypoglycemia ($15 min at <3.9 mmol/L three or more times per week) randomly assigned to two treatment periods of 4 weeks of self-administered subcutaneous dasi-glucagon at 120 lg or placebo. The primary and key secondary outcomes were continuous glucose monitor–captured percentage of time in level 1 and 2 hypoglycemia (<3.9 and <3.0 mmol/L), respectively. RESULTS Compared with placebo, treatment with dasiglucagon significantly reduced time in level 1 hypoglycemia by 33% (21.2 percentage points; 95% CI 22.0 to 20.5; P = 0.002) and time in level 2 hypoglycemia by 54% (20.4 percentage points; 95% CI 20.6 to 20.2; P < 0.0001). Furthermore, dasiglucagon corrected hypoglycemia within 15 min in 401 of 412 self-administrations, compared with 104 of 357 placebo self-administrations (97.3% vs. 29.1% correction of hypoglycemia rate; P < 0.001). Dasiglucagon was gener-ally well tolerated, with mostly mild to moderate adverse events of nausea. CONCLUSIONS Compared with placebo, 4 weeks of self-administered dasiglucagon effectively reduced clinically relevant hypoglycemia in individuals who had undergone Roux-en-Y gastric bypass surgery.