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Although prior studies have evaluated the role of sampling errors associated with local and regional methods to estimate peak flow quantiles, the investigation of epistemic errors is more difficult because the underlying properties of the random variable have been prescribed using ad-hoc characterizations of the regional distributions of peak flows. This study addresses this challenge using representations of regional peak flow distributions derived from a combined framework of stochastic storm transposition, radar rainfall observations, and distributed hydrologic modeling. The authors evaluated four commonly used peak flow quantile estimation methods using synthetic peak flows at 5,000 sites in the Turkey River watershed in Iowa, USA. They first used at-site flood frequency analysis using the Pearson Type III distribution with L-moments. The authors then pooled regional information using (1) the index flood method, (2) the quantile regression technique, and (3) the parameter regression. This approach allowed quantification of error components stemming from epistemic assumptions, parameter estimation method, sample size, and, in the regional approaches, the number of pooled sites. The results demonstrate that the inability to capture the spatial variability of the skewness of the peak flows dominates epistemic error for regional methods. We concluded that, in the study basin, this variability could be partially explained by river network structure and the predominant orientation of the watershed. The general approach used in this study is promising in that it brings new tools and sources of data to the study of the old hydrologic problem of flood frequency analysis.