Background: Bariatric surgery as treatment of obesity is increasing worldwide. No guidelines exist on which type of bariatric procedure to choose for the individual patient. Objectives: This study aims to compare Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) with respect to weight loss, complications, comorbidities, and quality of life. Setting: A nationwide multi-center register-based cohort study. Methods: We identified 16,053 patients treated by bariatric surgery from 2008 to 2021 (RYGB, n = 13,075; SG, n = 2978) from the Danish quality registry for treatment of severe obesity (DBSO). We calculated risk ratios (RRs) and prevalence ratios (PRs) comparing surgical complications, weight loss, and medical comorbidities by type of procedure up to 2 years after surgery. Results: Patients treated with RYGB experienced a greater weight loss than patients treated by SG both after 1 year (PR, .53; 95% confidence interval [CI], .48–.58) and 2 years (PR, .46; 95% CI, .39–.54). Compared with RYGB, SG yielded a lower risk of readmission (RR, .71; 95% CI, .60–.85). Likewise, the risk of reoperation between 30 days and 1 year (RR, .40; 95% CI, .30–.53) and 1 and 5 years (RR, .15; 95% CI, .12–.20]) were lower following SG. At 1-year follow-up, 76% of patients treated with RYGB and 63% of patients treated with SG experienced diabetes remission. Ten percent and 61% of patients were lost to follow-up after 1 and 2 years, respectively. Conclusion: The DBSO is an important resource in studying treatment of severe obesity. Weight loss is slightly greater after RYGB than after SG, but RYGB is associated with more frequent readmissions and reoperations.