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Two USEPA Regional Laboratories developed direct-injection LC/MS/MS methods to measure Pharmaceuticals and Personal Care Products (PPCPs) in water matrices. Combined, the laboratories were prepared to analyze 185 PPCPs (with 74 overlapping) belonging to more than 20 therapeutical categories with reporting limits at low part-per-trillion. In partnership with Suffolk County in NY, the laboratories conducted PPCP analysis on 72 samples belonging to 4 Water Systems (WS). Samples were collected at different stages of the WS (hospital effluents, WWTP influents/effluents) to assess PPCP relevance in hospital discharges, impact on WWTP performance and potential ecological risk posed by analytes not eliminated during treatment. Major findings include: a) acceptable accuracy between the two laboratories for most overlapping PPCPs with better agreement for higher concentrations; b) the measurement of PPCPs throughout all investigated WSwith total PPCP concentrations ranging between 324 and 965 mu g L-1 for hospital effluent, 259 and 573 mu g L-1 forWWTP influent and 19 and 118 mu g L-1 for WWTP effluent; c) the variable contribution of hospital effluents to the PPCP loads into the WWTP influents (contribution ranging between 1% (WS-2) and 59% (WS-3); d) the PPCP load reduction after treatment for all WS reaching more than 95% for WS using activated sludge processes (WS-2 and WS-4), with inflow above 6500m(3) d(-1), and having a lower percentage of hospital effluent in theWWTP influent; e) the relevance of four therapeutical categories for the PPCP load inWWTP effluents (analgesics, antidiabetics, antiepileptics and psychoanaleptics); and f) the risk quotients calculated using screening-level Predicted Non Effect Concentration indicate thatWWTP effluents contain 33 PPCPs with potential medium to high ecological risk. To our knowledge no other monitoring investigation published in the scientific literature uses direct-injection methods to cover as many PPCPs and therapeutical categories in different types of WS. (C) 2015 Elsevier B.V. All rights reserved.