<div><p>Background</p><p>Mortality from ischemic stroke has declined over time. However, little is known about the reasons for the decreased mortality. We therefore aimed to evaluate trends in in-hospital mortality and to identify factors associated with these trends.</p><p>Methods</p><p>This study was based on a prospective database of 26 hospitals of the Stroke Register of Northwestern Germany, which included 73,614 patients admitted between 2000 and 2011. Time trends in observed (crude) and risk-adjusted in-hospital mortality were assessed. Independent factors associated with death after stroke were evaluated using multivariable logistic regression analysis.</p><p>Results</p><p>The observed in-hospital mortality decreased from 6.6% in 2000 to 4.6% in 2008 (P < 0.001 for trend) and then remained fairly stable. The risk-adjusted mortality decreased from 2.85% in 2000 to 1.86% in 2008 (P < 0.01 for trend) and then increased to 2.32% in 2011. Use of in-hospital treatments including antiplatelets within 48 hours, antihypertensive therapy, statins, antidiabetics, physiotherapy and anticoagulants increased over time and was significantly associated with a decrease in mortality. The association of the year of admission with mortality became insignificant after adjustment for antiplatelet therapy within 48 hours (from OR 0.96; 95% CI, 0.94-0.98, to OR 0.99; 95% CI, 0.97-1.01) and physiotherapy (from OR 0.96; 95% CI, 0.94-0.97, to OR 0.99; 95% CI, 0.97-1.00).</p><p>Conclusions</p><p>In-hospital mortality decreased by approximately one third between 2000 and 2008. This decline was paralleled by improvements in different in-hospital managements, and we demonstrated that it was partly mediated by early antiplatelet therapy and physiotherapy use.</p></div