Polydimethylsiloxane (PDMS) is an elastomer commonly used in biomedical, microfluidic devices, and numerous other applications. However, PDMS binds blood serum protein due to its hydrophobic nature. The research described here investigates PDMS surfaces modifications that increase biocompatibility by covalently modifying the surface with 2-[methoxy(polyethyleneoxy)propyl]trichlorosilane (PEG-Cl3). Initial oxidation of the surface by UV treatment was followed by deposition of PEG-Cl3 using several different methods to eliminate dynamic surface restructuring leading to hydrophobic recovery. These methods included aqueous, vapor, and organic solvent deposition of PEG-Cl3. It was shown that these treatments stabilized the hydrophilic nature of the PDMS originally reached by UV light modification. It was also shown that these modifications are effective in repelling blood serum proteins such as fibrinogen and bovine serum albumin (BSA). Additional findings indicate that storage of the modified samples in an aqueous solution maintains the hydrophilic surface to an even greater extent.