The focus of the current study was to overcome the obstacles to incorporating non-steroidal anti-inflammatory drugs (NSAIDs) into a medical silicone elastomer and to investigate how the physicochemical properties of the drugs affect the curing process and drug release. Five representative NSAIDs were selected with different molecular weights and physicochemical properties. Silicone blends with 1% (w/w) drug in the sodium salt form could be obtained in a fully cured medical elastomer matrix whereas drugs in various other salt forms or the free acid form interfered with the curing process. The release rate was mainly dependent on the solubility in the drug-salt elastomer matrix, with ibuprofen sodium showing the fastest rate. These results indicate that inclusion of the NSAID salts in the silicone matrix does not change the microstructure or the permeability of the silicone matrix, and channel formation is minimal. The properties of NSAID-containing silicone blends are compatible with processes used for the manufacture of medical devices from silicone such as silicone stents or catheters, and could therefore be considered for such devices to reduce inflammation at the site of an implant and also for local delivery.