Various pharmaceuticals are essential for livestock farming, but some are highly toxic to aquatic life if they reach surface water bodies. Mediterranean Climate is characterized by dry summers followed by intense autumn storms. We studied the effect of these climatic conditions on the risk of pharmaceutical residues transfer to streams at the catchment-scale. Pharmaceutical products routinely used in the study area, as well as their application frequency and season, were identified through interviews with farmers. As a proof a concept, three veterinary pharmaceuticals (Fenbendazole (FBZ), Mebendazole (MBZ) and Ivermectin (IVM)) were chosen as model chemicals based on their relatively high usage, their specificity to represent different types of livestock (swine, sheep and cattle), and their ability to be analyzed using the same analytical method. Stream water was analyzed during low flow periods and at high frequency (up to 2 h−1) during flood events. The selected veterinary pharmaceuticals were not detected during low flow, but FBZ and MBZ reached high concentrations for short periods during floods. Due to the event-driven nature of their transfer, a significant load of veterinary pharmaceuticals can reach the river and cause temporary but significant degradation of water quality (e.g. for FBZ, the water concentration reached up to 355 times the predicted no effect concentration (PNEC)). This indicates that special care should be taken to avoid keeping freshly treated livestock on pastures that may become hydrologically connected under wet conditions. In addition, it suggests that low-frequency monitoring is not sufficient to detect those high concentration levels that exist during very short periods.