Stenting has become the first-line treatment of obstructive venous disease because of poor results of balloon angioplasty. This preclinical study aimed to investigate the safety and efficacy profile of a novel compliant venous scaffold (CVS), the Petalo (Catania, Italy) CVS (Fig), specifically designed for truncular venous malformations. Twelve healthy pigs weighing 90 kg were used to test the Petalo CVS. The devices were implanted into the internal jugular veins using a common femoral vein percutaneous approach. The safety profile including the success rate of device releasing, anchoring, and positioning was evaluated immediately. Fracture, migration, primary patency, and endothelial response were assessed at 1 month, 2 months, 3 months, and 6 months after the study procedure. A total of 32 devices were successfully released in both internal jugular veins. The positioning was precise, and no immediate migration occurred. In all cases, the devices were able to control the leaflets of the valve. No procedure- or device-related complications were reported, and all pigs successfully completed the different scheduled follow-up periods. The primary patency rate was 100%, and no fracture or migration of the device into the brachiocephalic trunk was reported. Histologic examination revealed only minimal lesions with minimal or absent inflammatory reaction surrounding the incorporated metallic rods. This porcine model study showed a promising safety and efficacy profile of Petalo CVS, a novel device based on venous concepts. The 6-month primary patency and absence of complications support the feasibility of a clinical trial for the treatment of truncular venous malformations in humans.