Laparoscopic Roux-en-Y gastric bypass (LRYGB) and laparoscopic vertical sleeve gastrectomy (LVSG) have been proposed as cost-effective strategies to manage obesity-related chronic disease. The aim of this systematic review was to study the peer review literature regarding postoperative nondiabetic comorbid disease resolution or improvement reported from randomized controlled trials (RCTs) comparing LVSG and LRYGB procedures. RCTs comparing postoperative comorbid disease resolution such as hypertension, dyslipidemia, obstructive sleep apnea, joint and musculoskeletal conditions, gastroesophageal reflux disease, and menstrual irregularities following LVSG and LRYGB were included for analysis. The studies were selected from PubMed, Medline, EMBASE, Science Citation Index, Current Contents, and the Cochrane database and reported on at least one comorbidity resolution or improvement. The present work was undertaken according to the Preferred Reporting Items of Systematic Reviews and Meta-Analyses (PRISMA). The Jadad method for assessment of methodological quality was applied to the included studies. Six RCTs performed between 2005 and 2015 involving a total of 695 patients (LVSG n = 347, LRYGB n = 348) reported on the resolution or improvement of comorbid disease following LVSG and LRYGB procedures. Both bariatric procedures provide effective and almost comparable results in improving or resolving these comorbidities. This systematic review of RCTs suggests that both LVSG and LRYGB are effective in resolving or improving preoperative nondiabetic comorbid diseases in obese patients. While results are not conclusive at this time, LRYGB may provide superior results compared to LVSG in mediating the remission and/or improvement in some conditions such as dyslipidemia and arthritis.