Abstract This study evaluated the capacity of a pilot-scale high-rate algal pond (HRAP) to remove pharmaceutical compounds (PCs) from domestic wastewater in the city of Santiago de Cali, Colombia. The compounds analyzed included antiepileptics, hypolipidemic drugs, tranquilizers and analgesics, and anti-inflammatory drugs. The HRAP operated under a continuous water flow of 0.2 m3d−1 and a 3-day hydraulic retention time (HRT). Removal efficiencies were high (>70%) for fenofibric acid, ibuprofen, and paracetamol; medium (30–70%) for gabapentin, lamotrigine, fenofibrate, gemfibrozil, diclofenac, ketoprofen, naproxen, and pentoxifylline; and low (<30%) for carbamazepine and its metabolite 10,11-Dihidro-10,11-dihidroxicarbamazepine (CBZ-Diol). The findings herein are similar to other studies, but were obtained with a shorter HRT. These results show that tropical environmental conditions favor photodegradation and contribute to the development of microalgae and the biodegradation process. Twenty microalgae species were identified, with the phylum Chlorophyta as the most abundant, particularly due to its natural introduction. The removal of the PCs also reflected a percentage reduction (>50%) in the ecological hazard posed by most of the compounds, although it is important to note that the hazard from gemfibrozil and ibuprofen remained high even after treatment, indicating the need for complementary treatment.