Ultraviolet radiation (UV)-activated peroxydisulfate (PDS) and peroxymonosulfate (PMS) advanced oxidation processes were examined for their capacity to remove nine pharmaceutically active compounds (PhACs) from secondary effluent. The effect of operational parameters (initial oxidant concentration, UV exposure time, pH, common coexisting anions and effluent organic matter (EfOM)) on UV/PDS and UV/PMS treatment efficiency was investigated in a collimated beam device housing a low-pressure mercury UV lamp emitting light at 253.7 nm. Both AOPs achieved high removals (>90%) when applied to pure water. Under otherwise similar conditions the removal percentage fell by 20–30% due to the scavenging of effluent organic matter (EfOM) in secondary effluent. Finally, eliminating EfOM but maintaining the inorganic composition, the radical scavenging effect was reduced and 98.3% and 85.6% average removals were obtained by UV/PDS and UV/PMS, respectively. Increasing pH improved degradation of several PhACs containing amine groups. Higher oxidant dosages created only a significant benefit in UV/PDS. The chloride anion produced a negligible effect on both processes, while higher nitrate concentrations increased removal percentage but did not affect degradation rate constants. Finally and surprisingly, the addition of bicarbonate had the strongest positive impact on the degradation kinetics observed, even stronger than the elimination of EfOM from secondary effluent.