Water quality trading has been proposed as a cost-effective approach for reducing nutrient loads through credit generation from agricultural or point source reductions sold to buyers facing costly options. We present a systematic approach to determine attenuation coefficients and their uncertainty. Using a process-based model, we determine attenuation with safety margins at many watersheds for total nitrogen (TN) and total phosphorus (TP) loads as they transport from point of load reduction to the credit buyer. TN and TP in-stream attenuation generally increases with decreasing mean river flow; smaller rivers in the modeled region of the Ohio River Basin had TN attenuation factors per km, including safety margins, of 0.19-1.6%, medium rivers of 0.14-1.2%, large rivers of 0.13-1.1%, and very large rivers of 0.04-0.42%. Attenuation in ditches transporting nutrients from farms to receiving rivers is 0.4%/km for TN, while for TP attenuation in ditches can be up to 2%/km. A 95 percentile safety margin of 30-40% for TN and 6-10% for TP, applied to the attenuation per km factors, was determined from the in-stream sensitivity of load reductions to watershed model parameters. For perspective, over 50 km a 1% per km factor would result in 50% attenuation = 2:1 trading ratio.