Objective Inadequate peripheral venous drainage during minimally invasive cardiac surgery (MICS) is a challenge and cannot always be solved with increased vacuum or increased centrifugal pump speed. The present study was designed to assess the benefit of virtually wall-less transfemoral venous cannulas during MICS. Methods Transfemoral venous cannulation with virtually wall-less cannulas (3/8″ 24F 530–630-mm ST) was performed in 10 consecutive patients (59 ± 10 years, 8 males, 2 females) undergoing MICS for mitral (6), aortic (3), and other (4) procedures (combinations possible). Before transfemoral insertion of wall-less cannulas, a guidewire was positioned in the superior vena cava under echocardiographic control. The wall-less cannula was then fed over the wire and connected to a minimal extracorporeal system. Vacuum assist was used to reach a target flow of 2.4 l/min per m² with augmented venous drainage at less than −80 mm Hg. Results Wall-less venous cannulas measuring either 630 mm (n = 8) in length or 530 mm (n = 2) were successfully implanted in all patients. For a body size of 173 ± 11 cm and a body weight of 78 ± 26 kg, the calculated body surface area was 1.94 ± 0.32 m². As a result, the estimated target flow was 4.66 ± 0.78 l/min, whereas the achieved flow accounted for 4.98 ± 0.69 l/min (107% of target) at a vacuum level of 21.3 ± 16.4 mm Hg. Excellent exposure and “dry” intracardiac surgical field resulted. Conclusions The performance of virtually wall-less venous cannulas designed for augmented peripheral venous drainage was tested in MICS and provided excellent flows at minimal vacuum levels, confirming an increased performance over traditional thin wall cannulas. Superior results can be expected for routine use.