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Venous drainage in cardiopulmonary bypass is a very important factor for safe cardiac surgery. However, the ideal shape of venous drainage cannula has not been determined. In the present study, we evaluated the effect of side-hole number under fixed total area and venous drainage flow to elucidate the effect of increasing the side-hole numbers.Computed simulation of venous drainage was performed. Cannulas were divided into six models: an end-hole model (EH) and models containing four (4SH), six (6SH), eight (8SH), 10 (10SH) or 12 side-holes (12SH). Total orifice area of the side-holes was fixed to 120 mm2 on each side-hole cannula. The end-hole orifice area was 36.3 mm2. The total area of the side-holes was kept constant when the number of side-holes was increased.The mean venous drainage flow rate of the EH, 4SH, 6SH, 8SH, 10SH and 12SH was 2.57, 2.52, 2.51, 2.50, 2.49, 2.41 L/min, respectively. The mean flow rate decreased in accordance with the increased number of side-holes.We speculate that flow separation at the most proximal site of the side-hole induces stagnation of flow and induces energy loss. This flow separation may hamper the main stream from the end-hole inlet, which is most effective with low shear stress. The EH cannula was associated with the best flow rate and flow profile. However, by increasing side-hole numbers, flow separation occurs on each side-hole, resulting in more energy loss than the EH cannula and flow rate reduction.