We report on patterns and trends in polybrominated diphenyl ethers (PBDEs) in the plasma of 284 bald eagle nestlings sampled between 1995 and 2011 at six study areas in the upper Midwestern United States. Geometric mean concentrations of total PBDEs (Σ of nine congeners) ranged from 1.78 ng/mL in the upper St. Croix River watershed to 12.0 ng/mL on the Mississippi River. Lake Superior nestlings fell between these two extremes. Between 2006 and 2011, trends differed among study areas with three declining, two remaining stable, and one increasing. Variation in ΣPBDE trends among study areas was linked to trends in individual congeners. The lower brominated PBDEs (BDE-47, -99, and -100) declined 4-10% while the higher brominated congeners (BDE-153 and -154) increased by about 7.0% annually from 2006 to 2011. This increase was the greatest in nestlings from the St. Croix River and below its confluence with the Mississippi River. Region-wide, our data suggest ΣPBDEs increased in bald eagle nestlings from 1995 through the mid-2000s and then declined by 5.5% annually from 2006 to 2011. These regional trends are consistent with the removal of penta- and octa-PBDEs from the global market.