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Background: Post-stroke depression has been shown to have a negative impact on patients’ quality of life but data regarding the relationship between pre-stroke depression and post-stroke outcomes are lacking.Methods: Patient reported outcome measures (PROMS) were prospectively collected (January 2014 – December 2014) as a part of PROSPER, a PCORI-funded study designed by researchers and stroke survivors to evaluate the effectiveness of therapies post-stroke. PROMS evaluated in the study included modified Rankin Scale (mRS) assessed at discharge, 3 months and 6 months post-discharge. EuroQual-5D-3L (EQ-5D-3L), EuroQual Visual Analog Scale (EQ-VAS), Patient Health Questionnaire-2 (PHQ-2), Stroke Impact Scale-16 (SIS-16), and Fatigue Severity Scale (FSS) were assessed at 3 months and 6 months post-discharge. Pre-stroke depression was identified from patient medical history. Validated dichotomized endpoints were used to create regression models to examine association of pre-stroke depression with PROMS.Results: Of 1,617 enrolled patients at 60 hospitals, 185 (11.4%) had pre-stroke depression. Patients with documented pre-stroke depression were more likely to be white, female and have a higher prevalence of cardiovascular risk factors than those without pre-stroke depression. While both cohorts had similar stroke severity and functional status at discharge, patients with pre-stroke depression had significantly worse PROMS at 3 months and 6 months post-discharge. Pre-stroke depression was associated with 56% higher odds of functional decline between 3 months and 6 months post-discharge with greater negative impact of stroke on patient’s health and life, and with increased likelihood of reporting severe fatigue during stroke recovery (Table 1).Conclusions: Pre-stroke depression is associated with worse patient reported outcomes and greater odds of functional decline after ischemic stroke discharge. Strategies to more effectively manage comorbid depression and improve outcomes in these patients are needed.