Survival and cause-specific mortality of female white-tailed deer (Odocoileus virginianus) have been well documented in forested and agricultural landscapes, but limited information has been collected in grassland habitats typical of the Northern Great Plains. Our objectives were to document and compare survival and cause-specific mortality of adult female white-tailed deer in four distinct ecoregions. We captured and radiocollared 190 (159 adult, 31 yearling) female white-tailed deer and monitored (including deer from a previous study) a total of 246 (215 adult, 31 yearling) deer from Jan. 2000 to Dec. 2007. We documented 113 mortalities; hunting (including wounding loss) accounted for 69.9% of all mortalities and vehicle collisions accounted for an additional 15.0%. Natural causes (e.g., disease, predation) of mortality were minor compared to human-related causes (e.g., hunting, vehicle collisions). We used known fate modeling in program MARK to estimate survival rates and compare ecoregions and seasons. Model {S_{season (winter = summer)}} had the lowest AIC_c value suggesting that survival differed only between seasons where winter and summer survival was equal and differed with fall season. Annual and seasonal (summer, fall, winter) survival rates using the top model {S_{season (summer = winter)}} were 0.76 (95% ci  =  0.70–0.80), 0.97 (95% ci  =  0.96–0.98), 0.80 (95% ci  =  0.76–0.83) and 0.97 (95% ci  =  0.96–0.98), respectively. High human-related mortality was likely associated with limited permanent cover, extensive road networks and high hunter density. Deer management in four distinct ecoregions relies on hunter harvest to maintain deer populations within state management goals.