A national-scale survey of 247 contaminants of emerging concern (CECs), including organic and inorganic chemical compounds, andmicrobial contaminants, was conducted in source and treated drinkingwater samples from 25 treatment plants across the United States.Multiplemethodswere used to determine these CECs, including six analytical methods tomeasure 174 pharmaceuticals, personal care products, and pesticides. A three-component quality assurance/quality control (QA/QC) programwas designed for the subset of 174 CECswhich allowed us to assess and compare performances of themethods used. The three components included: 1) a common field QA/ QC protocol and sample design, 2) individual investigator-developed method-specific QA/QC protocols, and 3) a suite of 46method comparison analytes thatwere determined in two or more analytical methods. Overallmethod performance for the 174 organic chemical CECs was assessed by comparing spiked recoveries in reagent, source, and treated water over a two-year period. In addition to the 247 CECs reported in the larger drinking water study, another 48 pharmaceutical compoundsmeasured did not consistentlymeet predetermined quality standards. Methodologies that did not seem suitable for these analytes are overviewed. The need to exclude analytes based on method performance demonstrates the importance of additional QA/QC protocols.