Relative benefits of coronary artery bypass (CABG) using single and multiple arterial grafting (SAG, MAG) and drug eluting stent (DES) in multivessel coronary disease remain uncertain. We compared SAG, MAG, and DES in a pairwise and network meta-analysis. Randomized trials and adjusted observational studies comparing CABG versus DES were included (primary end point: long-term mortality; secondary end points: operative mortality, perioperative stroke, and follow-up repeated revascularization [RR]). Studies with ≥1.7 arterial grafts and/or patient were classified as MAG. Bayesian network meta-analyses and random-model pairwise meta-analyses were performed. A total of 53,239 patients (8 randomized, 17 observational studies) were included (26,306 DES; 26,933 CABG). In pairwise comparison (mean follow-up: 5.42 years), CABG (MAG + SAG) was associated with lower long-term mortality (incident rate ratio [IRR] 0.77, 95% confidence interval [CI] 0.66 to 0.90), lower RR (IRR 0.37, 95% CI 0.27 to 0.51), increased perioperative stroke (odds ratio [OR] 3.18, 95% CI 1.70 to 5.97), and similar operative mortality (OR 1.04, 95% CI 0.64 to 1.70) compared with DES. There was a nonsignificant trend toward lower long-term mortality for studies with higher mean number of arterial grafts. In network meta-analyses, compared with DES, MAG was associated with lower long-term mortality (IRR 0.72, 95% credible interval [CrI] 0.57 to 0.92) and late RR (IRR 0.32, 95% CrI 0.21 to 0.49), SAG was associated with lower long-term mortality and RR (IRR 0.80, 95% CrI 0.66 to 0.97 and IRR 0.42, 95% CrI 0.29 to 0.61, respectively). In conclusion, CABG was associated with reduced 5-year mortality and need for RR compared with DES. MAG was ranked as the best treatment for the primary and all secondary outcomes.