A restrictive transfusion strategy led us to routinely try to conduct donor-blood free open-heart surgery even in neonates. The cardio-pulmonary bypass (CPB) circuit was minimized by priming volumina at 73 ml for the smallest patients with body weight up to 2.5 kg and 85–95 ml for those with body weight of more than 2.5 kg, and by positioning the console as close as possible to operation table. Measures were applied to save blood during the procedure. Transfusion threshold of 8 g/dl hemoglobin was retained. Effort was made to avoid transfusion while on CPB or to postpone transfusion towards CPB end. From 2013 to 2015, 149 consecutive neonates underwent 150 open-heart procedures without blood in priming volume. Weight was lower than 2.5 kg in five instances. The most frequent operations were arterial switch operation (n = 54) and Norwood procedure (n = 17). Transfusion-free operation was achieved in 44 procedures. The great majority (42/44 = 95%) involved biventricular repair and included 50% (27/54) of arterial switch operations. 106 patients were transfused: 63 mostly towards CPB end, and 43 after coming off bypass. Transfusion-free procedures were associated with postoperative lower lactate concentration (p = 0.0013) and shorter duration of mechanical ventilation (p = 0.0009). Seven patients were discharged from hospital without getting any transfusion of blood or blood products. In conclusion, routine application of bloodless priming in neonatal cardiopulmonary bypass is safe and beneficial. It results into a good number (29%= 44/150) of transfusion-free operations. Postponing transfusion towards CPB end favors an overall restrictive transfusion strategy for all patients.