In this case study pharmaceuticals were analysed in the Mondego river (Portugal) and their environmental risk assessed by means of risk quotients based on an extensive retrieval of ecotoxicological data for freshwater and saltwater species. The Mondego river crosses Coimbra, the most populated city in the Portuguese Centro Region hosting a complex of regional hospitals. Environmentally relevant and prioritised pharmaceuticals were investigated in this study and their potential hazards were evaluated by conducting a separate risk assessment for the freshwater and estuary parts of the examined river section.A target analysis approach with method detection limits down to 0.01 ng L−1 was used to determine pharmaceuticals. Twenty-one prioritised target analytes out of seven therapeutical classes (antibiotics, iodinated X-ray contrast media (ICM), analgesics, lipid reducers, antiepileptics, anticonvulsants, beta-blockers) were investigated by applying ultra-high pressure liquid chromatography coupled to a triple quadrupole mass spectrometer equipped with an electrospray ionisation source.The relative pattern of pharmaceuticals along the middle to the lower Mondego showed a quite uniform picture while an approximately 40fold increase of absolute concentrations was observed downstream of the wastewater treatment plant (WWTP) discharge of Coimbra. The most frequently measured substance groups were the ICM, represented by the non-ionic ICM iopromide (βmin: 3.03 ng L−1 - βmax: 2,810 ng L−1). Environmentally more critical substances such as carbamazepine, diclofenac, and bezafibrate, with concentrations up to and 52.6 ng L−1, 59.8 ng L−1, and 10.2 ng L−1 respectively, may potentially affect aquatic wildlife. Carbamazepine revealed elevated risk quotients (RQs >1) along the middle and lower Mondego with a maximum RQ of 53 downstream of Coimbra. Especially for saltwater species, carbamazepine and clarithromycin pose high potential risks.Especially in periods of low water discharge of the Mondego river, other pharmaceuticals as diclofenac and bezafibrate may pose additional risks downstream of the WWTP.