Cultural eutrophication of surface waters has become a major source of water-quality impairment throughout the US. In response, the US Environmental Protection Agency (USEPA) has devised a national strategy for the development of regional nutrient criteria. Our study is part of New York State's effort to revise its narrative nutrient standard for N and P and is based on the USEPA's recommended weight-of-evidence approach. The objective of our investigation was to identify nutrient thresholds based on a final weighted average of results from percentile analysis, nonparametric deviance reduction (changepoint), and cluster analysis. The thresholds were determined from shifts in biological community structure (benthic macroinvertebrate and diatom) related to water-column nutrient data from 40 large river sites throughout New York State. USEPA's percentile analysis yielded possible criteria of 0.023 mg total P (TP)/L, 0.51 mg total N (TN)/L, 0.16 mg NO₃-N /L, and 2.4 mg chlorophyll a (chl a)/m³. Threshold responses in benthic macroinvertebrate metrics at the 50^th percentile occurred at concentrations between 0.009 and 0.07 mg TP/L, 0.41 and 1.2 mg TN/L, 0.18 and 0.55 mg NO₃-N/L, and 2.1 mg chl a/m³. Cluster analysis yielded 3 groups of sites based on macroinvertebrate and diatom taxa. The median nutrient values of the medium-nutrient-condition site clusters were used to set criteria for TP and TN. For site clusters based on macroinvertebrate data these values were 0.037 mg TP/L and 0.68 mg TN/L. For clusters based on diatom data these were 0.037 mg TP/L and 0.78 mg TN/L. Based on the weight-of-evidence approach and results from all 3 methods, the proposed guidance values for nutrients in large rivers are 0.03 mg TP/L, 0.7 mg TN/L, 0.3 mg NO₃-N/L, and 2.2 mg chl a/m³. These values are similar to those derived by others and provide meaningful nutrient endpoints that would be protective of aquatic life in large rivers.