Fluorinated polymers are widely used as biomaterials in various biomedical implant and device applications. However, thrombogenicity, surface-induced inflammation, and risk of microbial infection remain key issues that can limit their use. In this work, we describe the first nitric oxide (NO) releasing fluorinated polymer, in which a new fluorinated NO donor, S-nitroso-N-pentafluoropropionylpenicillamine (C2F5-SNAP), is incorporated within the polyvinylidene fluoride (PVDF) tubing. The synthesis, decomposition kinetics, and NO-release characteristics of the C2F5-SNAP species are described in detail. Then, using a simple solvent swelling method, we demonstrate that C2F5-SNAP can readily be doped into PVDF tubing. The resulting tubing can release NO for 11 days under physiological conditions, with an NO flux > 0.5 × 10-10 mol/cm2·min over the first 7 days. Due to fluorous-fluorous interactions, the leaching of the fluorinated NO donor and its decomposed products is shown to be very low (less than 5 nmol/mg, total). Further, the new NO-releasing PVDF tubing exhibits significant antimicrobial activity (compared to undoped PVDF tubing) against both gram positive and negative S. aureus and P. aeruginosa bacterial strains over a 7 d test period. This new NO-releasing fluorinated polymer is likely to have the potential to improve the biocompatibility and antimicrobial activity of various biomedical devices.