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A medium-pressure (MP) ultraviolet (UV) system was used to investigate the UV photolysis and UV/H₂O₂ oxidation of pharmaceutically active compounds (PhACs) that belong to different therapeutic classes and were found to occur in the aquatic environment. The results obtained in laboratory-grade water (LGW) and surface water (SW) were compared with low-pressure (LP) results reported previously. Overall, MP lamps proved to be more efficient to maximize the bench-scale degradation of the selected group of compounds (ketoprofen, naproxen, carbamazepine, ciprofloxacin, clofibric acid, and iohexol) by both UV photolysis and UV/H₂O₂ oxidation. Fundamental direct and indirect photolysis parameters obtained in LGW are reported and used to model the MP-UV photolysis and MP-UV/H₂O₂ oxidation of the pharmaceuticals in SW, predicting the experimental results very well.