Accurate estimation of nutrient loads in rivers and streams is critical for many applications including determination of sources of nutrient loads in watersheds, evaluating long-term trends in loads, and estimating loading to downstream waterbodies. Since in many cases nutrient concentrations are measured on a weekly or monthly frequency, there is a need to estimate concentration and loads during periods when no data is available. The objectives of this study were to: (i) document the performance of a multiple regression model to predict loads of nitrate and total phosphorus (TP) in Iowa rivers and streams; (ii) determine whether there is any systematic bias in the load prediction estimates for nitrate and TP; and (iii) evaluate streamflow and concentration factors that could affect the load prediction efficiency. A commonly cited rating curve regression is utilized to estimate riverine nitrate and TP loads for rivers in Iowa with watershed areas ranging from 17.4 to over 34,600 km². Forty-nine nitrate and 44 TP datasets each comprising 5–22 years of approximately weekly to monthly concentrations were examined. Three nitrate data sets had sample collection frequencies averaging about three samples per week. The accuracy and precision of annual and long term riverine load prediction was assessed by direct comparison of rating curve load predictions with observed daily loads. Significant positive bias of annual and long term nitrate loads was detected. Long term rating curve nitrate load predictions exceeded observed loads by 25% or more at 33% of the 49 measurement sites. No bias was found for TP load prediction although 15% of the 44 cases either underestimated or overestimate observed long-term loads by more than 25%. The rating curve was found to poorly characterize nitrate and phosphorus variation in some rivers.