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Cannula design is of prime importance for venous drainage during cardiopulmonary bypass (CPB). To evaluate cannulas intended for CPB, an in vitro circuit was set up with silicone tubing between the test cannula encased in a movable preload reservoir and another static reservoir. The pressure-drop (ΔP) value (P-drainage - P-preload) was measured using Millar pressure transducers. Flow rate (Q) was measured using an ultrasound flowmeter. Data display and data recording were controlled using a LabView application, custom made particularly for our experiments. Our results demonstrated that ΔP, Q, and cannula resistance (ΔP/Q) values were significantly decreased when the cannula diameter was increased for Smart and Medtronic cannulas. Smartcanula® showed 36% and 43% less resistance compared to Medtronic venous and Medtronic femoral cannulas, respectively.The cannula shape (straight- or curved-tips) did not affect the DLP cannula resistance. Out of five cannulas tested, the Smartcanula® outperforms the other commercially available cannulas. The mean (ΔP/Q) values were 3.3 ± 0.08, 4.07 ± 0.08, 5.58 ± 0.10, 5.74 ± 0.15, and 6.45 ± 0.15 for Smart, Medtronic, Edwards, Sarns, and Gambro cannulas, respectively (two-way ANOVA, p < 0.0001). In conclusion, the present assay allows discrimination between different forms of cannula with high or low lumen resistance.