OBJECTIVES: Minimally invasive cardiac surgery (MICS) struggles with effective caval isolation and cannulation for cardiopulmonary bypass (CPB). We aimed to develop a novel MICS venous cannula, eliminating external manipulations. The goal of this study is to thoroughly evaluate both the safety and the efficacy of a newly developed venous cannula. METHODS: The study presents the Aulus venous cannula for MICS, designed with internal balloons to block caval blood flow. Preclinical bench tests with a cardiac biosimulator and large animal studies per ISO10993-2016, evaluated performance and safety. RESULTS: The heparin-coated Aulus cannula had a post-sterilization comparable density of ∼0.200 μg/cm2. In ex vivo tests, using porcine heart models, the cannula enabled full caval occlusion, with endoscopic views confirming precise positioning. The pressure drop remained below the haemolytic threshold of 100 mmHg, indicated lower values compared to BioMedicus. A non-Good Laboratory Practice (GLP) large animal study included eight ovine models, divided into short- and long-term follow-up groups. Clinical pathology values were consistent CPB procedures, and histopathology indicated favourable tolerance despite short-term vessel injuries and long-term stenosis with fibrosis. CONCLUSIONS: The Aulus cannula showed effective anticoagulant activity, strong integrity, and good tolerance in vitro and in vivo, highlighting its clinical potential.