The accumulation of pharmaceuticals in the environment is of major concern, and efficient procedures are needed to eliminate them. Inorganic semiconductor photocatalysts, such as titanium dioxide, offer a promising solution. We compare the photocatalytic degradation of the two non‐steroidal anti‐inflammatory drugs ibuprofen (IBP) and naproxen (NPX) by TiO2 nanoparticles in water. Photocatalysts synthesized using different methods were evaluated and compared with commercially available Evonik‐P25 TiO2, and with direct photodegradation. The synthesized nanoparticles show high photocatalytic activity towards IBP (>97% degradation) and NPX (>90% degradation), and up to 79% mineralization is observed with NPX, and ca 50% with IBP. Major IBP photoproducts were 1‐(4‐isobutylphenyl)ethanol, 1‐(4‐isobutylphenyl)ethanone and 1‐(4‐ethylphenyl)‐2‐methylpropan‐1‐ol, while photocatalysis of NPX, showed the formation of 1‐(6‐methoxynaphthalen‐2‐yl)ethanol and 1‐(6‐methoxynaphthalen‐2‐yl)ethanone. The results were rationalized by considering one major primary pathway that involves initial decarboxylation of a chemisorbed compound followed by degradation of the radical intermediate produced. Our findings strongly suggest that with these compounds possessing carboxylic acid groups, the degradation mechanism involves competition between oxidative decarboxylation of chemisorbed compounds by semiconductor holes, and hydroxyl radical attack on physisorbed substrates.