Global bacterial infections associated with conventional polyvinyl chloride (PVC) medical devices place a heavy burden on healthcare systems and thus it will be desirable if medical devices are made from antimicrobial PVC. There are numerous studies focusing on polymer surface modifications to either leach antimicrobial agents or kill pathogenic microbes upon direct contact. In this work, mannitol fumarate ester‐based aluminum metal alkoxide (MFE‐Al) additive was developed to confer simultaneously improved antibacterial property and enhanced high temperature sterilization resistance of the resultant PVC. Data obtained confirm that the MFE‐Al stabilized PVC sheets significantly inhibit 98% bacterial growth. They also show biocompatibility with cultured H9C2 cardiomyocytes and hemocompatibility in vitro. Dry heat sterilization is generally not suitable for PVC medical wares due to their poor thermal compatibility. Surprisingly, our antimicrobial‐biocompatible PVC can maintain stability at 180°C for 90 min. Such a high thermal stability indicates the MFE‐Al stabilized PVC can endure 90 cycles of dry‐heat sterilization without significant damage. This study may provide a solution to reduce PVC medical waste for a maximum benefit without compromising human health or the environment.