This systematic review and meta-analysis compares the efficacy of COR-KNOT® automated fasteners to hand-tied knots in cardiac valve surgery. Analyzing data from 1,411 participants across eight observational studies and two randomized controlled trials, the findings indicate that COR-KNOT significantly reduces aortic cross-clamp (AXT) and cardiopulmonary bypass (CPB) times, as well as the incidences of valvular regurgitation and need for prolonged ventilatory support, without negatively impacting mortality, atrial fibrillation, left ventricular ejection fraction, or renal failure rates. These results support the use of COR-KNOT devices in cardiac surgery to enhance surgical efficiency and patient outcomes.