Background Symptomatic intracranial hemorrhage (sICH) occurs uncommonly after ischemic stroke therapy with Tissue plasminogen activator (TPA). Clotting factor administration may be a treatment option. Objective To determine if treatment with clotting factors was associated with improved outcomes in sICH. Methods We conducted a retrospective cohort study within University of Texas at Houston Stroke registry involving consecutive patients from February 1, 2007 to June 30, 2011 with TPA related sICH; including cases with subsequent intra-arterial therapy. Intervention clotting factor administration; fresh frozen plasma or cryoprecipitate. Outcomes modified Rankin Score mRS at discharge, death, and hematoma expansion. Results Of 921 patients treated with TPA, 48 (5.2%) had sICH and 45 met criteria for the study. Nineteen patients received clotting factors (42.2%) (18 received FFP and 7 received cryoprecipitate), while 26 (57.8%) patients received conservative management without clotting factors. None of the patients treated with clotting factors and only 2 of those who did not receive clotting factors had a good outcome; mRS ≤2. All the patients treated with clotting factors and most of those not treated were left bedridden or dead (mRS 4–6); 19 (100%) vs. 22 (85%). Mortality was 9 (47.4%) vs. 9 (34.6%) respectively. There was no difference in hematoma expansion between the two groups. Conclusions We found no evidence that treatment of sICH with clotting factors has a favorable effect on clinical or radiological outcomes. However, the sample was small due to the low frequency of sICH. New treatments are urgently needed for this uncommon yet serious condition.