Fetal bypass presents several perfusion challenges, including the need for high arterial flow rates using flexible arterial and small venous cannulae. We hypothesized that vacuum-assisted venous drainage (VAVD) would improve drainage and allow perfusion at higher flow rates which are thought to prevent placental dysfunction induced by fetal bypass. We conducted bypass for 60 minutes in 14 fetal lambs (90-105 days gestation; approximately 1-1.5 kg) using a roller pump and various angled venous cannulae (8-12 Fr). VAVD at -20 mm Hg or -40 mm Hg was compared with gravity drainage. Average flow using gravity drainage was 139 ml/kg/min; after VAVD, we achieved average flows of 285 ml/kg/min (range, 109-481 ml/kg/min). VAVD at -40 mm Hg caused right atrial trauma in four fetuses; no injury was seen at -20 mm Hg. Venous air entrainment during repair of the injuries did not result in any apparent air embolism. Spontaneous pulmonary hemorrhage occurred in two fetuses at the highest flows (> or = 400 ml/kg/min). In all but one case, termination of bypass was followed by placental dysfunction within 120 minutes. VAVD can be safely applied during fetal bypass provided pressures are kept < or = -20 mm Hg. However, the achieved higher flow rates do not prevent postbypass placental dysfunction and may indeed be detrimental to the fetus.