Background: Randomized-controlled trials of thrombolysis in ischemic stroke have poorly represented patients with pre-stroke disability and the benefit of thrombolysis in this population remains uncertain. We performed a systematic review and meta-analysis to examine the outcomes of thrombolysis in patients with pre-morbid disability. Methods: In accordance with MOOSE guidelines, we retrieved studies reporting intravenous thrombolysis (IVT) in patients with pre-stroke disability (mRS=3-5) with ischemic stroke, either compared to untreated patients or to treated patients without pre-morbid disability. Primary outcome was the return to pre-morbid disability at 90-days. Results: 8 articles were included involving 103,988 patients. Patients with disability treated with IVT had better odds of returning to baseline function compared to those who did not receive IVT (OR=7.26, 95%CI=2.51-21.02). Mortality and sICH were not significantly different between patients with disability receiving IVT or not. Favourable outcomes (mRS=0-2 or return to pre-morbid mRS) and sICH were not significantly different between patients with and without disability. Mortality was three times higher in those with pre-morbid disability treated with IVT (38.2% versus 12.6%). Conclusions: Thrombolysis in patients with disability was associated with better outcomes compared to patients not receiving IVT. High-quality data comparing treated versus untreated patients with pre-morbid disability is needed to clarify this issue.