Introduction We aim to review the available literature on morbidly obese patients treated with one anastomosis gastric bypass (OAGB) or Roux-en-Y gastric bypass (RYGB) in order to compare the clinical outcomes of the two methods. Methods A literature search was performed in PubMed, Cochrane Library, and Scopus, in accordance with the PRISMA guidelines. Results Sixteen studies were included in the qualitative analysis, and 11 studies were included in the quantitative analysis (meta-analysis), incorporating 12,445 patients. OAGB was associated with shorter mean operative time. The length of hospital stay was comparable between the two procedures. The incidence of leaks, marginal ulcer, dumping, bowel obstruction, revisions, and mortality was similar between the two approaches. The incidence of malnutrition was increased in patients treated with OAGB, while the incidence of internal hernia and bowel obstruction was greater in the RYGB group. In addition, the OAGB was associated with greater % excess weight loss (%EWL) at 1, 2, and 5 years postoperatively. The rate of diabetes remission was greater in the OAGB group. Nonetheless, the rate of hypertension and dyslipidemia remission was similar between OAGB and RYGB. Conclusion The present meta-analysis is the best currently available evidence on the topic and demonstrates the superiority of OAGB compared with RYGB, in terms of weight loss and diabetes remission. However, the OAGB was associated with a significantly higher incidence of malnutrition, thus indicating the significant malabsorptive traits of this operation.