Surgical and percutaneous coronary artery intervention revascularization are traditionally considered isolated options. A simultaneous hybrid approach may allow an opportunity to match the best strategy for a particular anatomic lesion. Concerns regarding safety and feasibility of such an approach exist. We examined the safety, feasibility, and early outcomes of a simultaneous hybrid revascularization strategy (minimally invasive direct coronary bypass grafting of the left anterior descending [LAD] artery and drug-eluting stent [DES] to non-LAD lesions) in 13 patients with multivessel coronary artery disease that underwent left internal mammary artery to LAD minimally invasive direct coronary bypass performed through a lateral thoracotomy, followed by stenting of non-LAD lesions, in a fluoroscopy-equipped operating room. Assessment of coagulation parameters was also undertaken. Inhospital and postdischarge outcomes of these patients were compared to a group of 26 propensity score matched parallel controls that underwent standard off-pump coronary artery bypass. Baseline characteristics were similar in both groups. All hybrid patients were successfully treated with DES and no inhospital mortality occurred in either group. Hybrid patients had a shorter length of stay (3.6 +/- 1.5 vs 6.3 +/- 2.3 days, P < .0001) and intubation times (0.5 +/- 1.3 vs 11.7 +/- 9.6 hours, P < .02). Despite aggressive anticoagulation and confirmed platelet inhibition, hybrid patients had less blood loss (581 +/- 402 vs 1242 +/- 941 mL, P < .05) and decreased transfusions (0.33 +/- 0.49 vs 1.47 +/- 1.53 U, P < .01). Six-month angiographic vessel patency and major adverse cardiac events were similar in the hybrid and off-pump coronary artery bypass groups. A simultaneous hybrid approach consisting of minimally invasive coronary artery bypass grafting with left internal mammary artery to LAD combined with revascularization of the remaining coronary targets using percutaneous coronary artery intervention with DES is a feasible option accomplished with acceptable clinical outcomes without increased bleeding risk.