Covalent surface modification of medical grade PVC tubing was performed using copper-free azide-alkyne cycloaddition reactions to prepare anti-fouling surfaces. PVC azide surface was synthesized by nucleophilic substitution of labile chlorine with sodium azide in the presence of phase transfer catalyst in aqueous media to minimize loss of plasticizer. Electron-poor alkynes with different functionality (zwitterionic, polyethylene oxide, polyfluoro and quaternary amines) were synthesized and covalently attached to the PVC azide surface by thermal azide-alkyne cycloaddition reactions. The reaction progress was monitored by ATR-FTIR spectroscopy. Static contact angle, surface free energy, contact angle hysteresis and atomic force microscopic images were taken for each modified surface. Except for the C6F13 polyfluoro group, the other functional groups containing zwitterionic, polyethylene oxide and quaternary ammonium display hydrophilic properties with the initial SCA in the range of 35-80° due to the strong surface charges. All the modified PVC surfaces maintain their wetting properties against vigorous water rinsing for long period of time (over 60 minutes of sonication) confirming strong covalent bonding of the functional groups to the surface. The antifouling activity of these modified endotracheal tubing samples was evaluated by bacterial adherence assay using Pseudomonas aeruginosa, a gram-negative opportunistic and nosocomial pathogen. Although the adherence assays demonstrate that high polyfluoro (di-ester of C6F13) and long quaternary amine functionality samples slightly reduced P. aeruginosa adherence to endotracheal tubing, the inhibition was not as strong as expected. X-Ray Photoelectron Spectroscopy revealed a pre-existing silicone coating on the original commercial samples, dampening the effects of biofilm inhibition from the chemical modification procedures.