score) between patients with IS and those without. Individuals with IS were more likely to have early radiographic evidence of intracranial mass effect (52%, IS patients vs. 40%, no IS; pZ0.003). At rehabilitation discharge, those with IS had lower FIMTM total scores (median 77, IS vs. 91, no IS; p<0.001), higher DRS scores (median 6.5, IS vs. 6.0, no IS; p<0.001), longer duration of PTA (median 49 days, IS vs. 30 days, no IS; p<0.001), and longer inpatient rehabilitation LOS (median 29 days, IS vs. 19 days, no IS; p<0.001). In multivariate analyses controlling for age, sex, initial clinical status and neuroanatomic injury characteristics, ischemic stroke predicted poorer outcome by all rehabilitation discharge measures assessed, accounting for a 13.6-point reduction in FIMTM total score (95% CI,-18.0,-9.2; p<0.001), a 1.7-point increase in DRS (95% CI, 0.975, 2.425; p<0.001), a 19.8-day increase in PTA duration (95% CI, 13.4,26.2; p<0.001), and a 12-day increase in LOS (95% CI, 7.2, 17.1; p<0.001). Conclusions: Ischemic stroke is observed in 2.5% of acute moderate to severe TBI patients, and predicts worse functional and cognitive outcome. These findings may help guide initial treatment decisions when IS is suspected after TBI, and help direct appropriate subsequent rehabilitation. Vigilance for stroke is warranted when associated signs or symptoms are observed acutely following TBI or polytrauma.