The use of streamflow simulations from the Vflo model and subsequent calculation of streamflow metrics to investigate flow-ecology relationships may be hindered by our inability to accurately model flow variability and extreme flows of the arid Great Plains. The Canadian River and other rivers in the Great Plains tend to have highly variable flows and harsh environmental conditions. The combination of these environmental conditions makes semi-arid and arid regions difficult to represent with a hydrologic model, especially extreme events. In some cases, overestimating flows may be acceptable to water managers (e.g., vulnerability of infrastructures), but could greatly affect estimates of fish species persistence. To address incidences where poor model performance affected metrics derived from Vflo simulations, we suggest three possible options. 1) Restrict flow-ecology relationships to the mainstem of the Canadian River below Lake Meredith, 2) Restrict assessments to streamflow data aggregated at a monthly time step (although typically, this does not match ecological processes well); 3) Focus on streamflow metrics with a high prediction accuracy (e.g., magnitude, timing and duration at some locations). To maximize the number of potential explanatory variables and survey locations available in the Canadian River basin for the development of flow-ecology response models and minimize bias and uncertainty, a combination of these approaches is likely warranted. To move forward on flow-ecology relationships with valid statistical power, the compiled fish data (see processing steps) is best combined with available gage data to improve the development of ecological relationships.