Ecological assessments of streams are incomplete without understanding whether the natural flow regime is intact.  Assessing hydrologic alteration (i.e., condition) requires that we quantify the attributes of the flow regime that would be expected in the absence of anthropogenic disturbance.  Our objective was to evaluate whether indicators of the natural flow regime could be predicted at regional and national spatial scales using geospatial data.  We first selected 1,272 gaged river basins throughout the contiguous U.S. where the hydrologic regimes were either least disturbed or near pristine.  Using the period of record for these sites, we calculated 13 hydrologic indicators of magnitude, frequency, duration, timing, and rate of change.  We used a robust modeling approach to evaluate the precision with which each indicator could be predicted with a single national and several regional models. We compared the precision of predictive models to that of “null” models, where expected values of each indicator were constant across hydrologic regions and ecoregions.  A single national predictive model produced the most precise estimates for most indicators.  Error rates ranged from 15-40%, but were <=25% for most indicators.  We selected three gaged, non-reference sites to illustrate how predictive models could be used to assess site-specific hydrologic condition.  These examples show how the model accurately estimates pre-disturbance hydrology and how reservoir construction and urbanization can affect hydrologic condition.