The advantage of the use of photocatalysts to treat persistent organic pollutants (POP) was demonstrated with the decomposition of trimethoprim (TRI), an antibiotic most frequently detected in municipal wastewaters and surface waters. In this study, the oxidation process by UV/TiO2 was employed as an alternative to advanced oxidation process (AOP) to remove residual antibiotics from water. High concentrations of TRI were used to study the efficiency of photocatalysis. Both batch and continuous photoreactors were used. The decomposition of TRI by TiO2/UV photooxidation occurred gradually over time. On the other hand, with UV irradiation alone, the reduction of TRI mineralization was relatively small. The effect of light intensity showed there was no significant impact of UV light intensity on the degradation of TRI in the range of increasing intensities studied. The simulation using first-order kinetics provided a good fit with the experimental data. In the continuous system, the feed flow rate was adjusted to maximize the percentage of mineralization of targeted compounds inside the photoreactor. A lower flow rate, i.e., higher detention time, achieved higher percentage of TRI mineralization. The results indicated that TiO2/UV irradiation was effective in removing TRI.