The presence of pharmaceutically active compounds (PhACs) in surface water is well known, whereas their natural occurrence in biota is much less explored. The aim of this work was to evaluate the bioaccumulation of PhACs in adult toads of the neotropical species Rhinella arenarum. Three sites were selected in Buenos Aires (Argentina): a reference site (Site 1), a site with direct discharge from a secondary wastewater treatment plant (WWTP) (Site 2) and a site 300 m downstream of the WWTP discharge (Site 3). Surface water samples, as well as muscle, liver and fat bodies of toads were collected, extracted and analyzed by LC-MS/MS. Highly significant differences in total PhACs concentration in surface water (p < 0.005) were detected between Site 2 and the other sites. These concentrations ranged from 0.37 to 52.46 ng/L at Site 1, 0.71–6950.37 ng/L at Site 2, and 0.12–75.45 ng/L at Site 3. In general, bioaccumulation of PhACs in toad tissues was similar between sites and tissues of each site. The highest concentrations were detected in the muscle of toads from Site 3 (1.06–87.24 ng/g dw), followed by liver (1.77–38.10 ng/g dw) and fat bodies (0.68–20.59 ng/g dw) from Site 1. Ibuprofen (6950 ng/L), acetaminophen (3277 ng/L) and valsartan (2504 ng/L) were the compounds with the highest concentrations in surface water from Site 2, whereas acetaminophen (87.2 ng/g dw, muscle from Site 3), desloratadine (38.1 ng/g dw, liver from Site 1), and phenazone (25.9 ng/g dw, liver from Site 1) were the ones that showed the highest concentrations in biota. This is the first time a field study has examined the environmental bioaccumulation of PhACs in anurans, demonstrating their potential for monitoring the status of natural ecosystems. Display omitted •Analgesics/anti-inflammatories showed the highest concentrations.•Antibiotics showed the highest frequencies of detection.•Twenty pharmaceuticals detected for the first time in surface water from Argentina.•Nearly thirty pharmaceuticals detected for the first time in adult anurans.•First field study to evaluate the bioaccumulation of pharmaceuticals in toads.