The purpose of this study was to examine the longitudinal safety and efficacy of hybrid coronary revascularization (HCR) in a large cohort of patients with multivessel coronary artery disease (CAD). From 2009 to 2020, 561 consecutive patients (median age 64.0 years, predicted risk of mortality 1.3% ± 1.8%, 403 with 2-vessel disease and 158 with 3-vessel disease) underwent a planned HCR procedure with a robot-assisted off-pump left internal mammary artery to left anterior descending (LIMA-LAD) coronary artery bypass graft (CABG) combined with percutaneous coronary intervention (PCI) of non-LAD vessels. Multivariable regression analysis was used to identify risk factors for short-term and longer-term outcomes. Operative mortality and stroke occurred in 4 (0.7%) and 5 patients (0.9%), respectively. Postoperative angiography revealed LIMA patency in 415 of 425 patients (98%). Median follow-up was 4.5 years and was 93% complete. Repeat revascularization occurred in 44 patients (8%) at a median of 2.7 years. Freedom from repeat revascularization and survival at 5 years was similar between patients with 2-vessel and 3-vessel disease (P = 0.73 and P = 0.19, respectively). Completely revascularized patients had 5-year survival of 91% versus 64% for incompletely revascularized patients (hazard ratio = 3.8, P < 0.001). Age (P = 0.03), renal failure (P < 0.001), and history of myocardial infarction (P = 0.01) were risk factors for late adverse events. HCR is a safe and effective minimally invasive alternative to conventional CABG or multivessel PCI with a low incidence of late repeat revascularization and mortality. HCR can be safely applied to carefully selected patients with either 2-vessel or 3-vessel CAD; however, incomplete revascularization may result in lower long-term survival.