This paper provides data on the occurrence of selected human pharmaceuticals (carbamazepine, clofibric acid, diclofenac, fenofibrate, fenoprofen, gemfibrozil, ibuprofen, ketoprofen, and naproxen) including steroid hormones (17β-estradiol, 17α-ethinylestradiol, and estrone) in influents/effluents to/from the four principal wastewater treatment plants (WWTPs) serving the city of Rome (Italy), in two different sampling campaigns. Target compounds were also analyzed in the receiving River Tiber and River Aniene. Analytical determination was carried out by LC-MS/MS after sample cleanup and concentration by off-line solid-phase extraction (SPE). The aim of the study was to increase the information currently available on the presence and persistence of pharmaceuticals in Italian urban wastewaters and to evaluate the environmental impact of the pharmaceutical residues discharged through effluents into the receiving rivers. Results indicated that after the treatment processes, most of pharmaceuticals were not completely eliminated, as average removal efficiencies were in the 14-100% wide range during both sampling periods, with higher yields in spring than in winter. Levels detected in overall samples ranged from 5 to 2,230 ng/L in influents and from 5 to 1,424 ng/L in effluents. Carbamazepine, diclofenac, ibuprofen, and gemfibrozil showed the highest persistence to removal. Concentrations in the receiving waters were about one order of magnitude lower than in effluents, with a tendency to increase progressively through the urban tract of the river. Finally, an environmental risk analysis showed that carbamazepine, gemfibrozil, and estrone can pose a high risk at the concentrations detected in effluents and a medium risk in rivers, highlighting their potential hazard for the health of the aquatic ecosystem.