Serum albumin levels has been shown to predict outcome in ischemic stroke patients. We aimed to investigate the relationship between serum albumin levels and hemorrhagic transformation (HT) after intravenous thrombolysis (IVT) in patients with acute stroke. 428 patients receiving intravenous rt-PA therapy were included from 2013 to 2016 and were categorized into two groups: low level (<35 mmol/L) and normal level (35-55 mmol/L) group. Demographic, clinical and laboratory information, HT and functional outcomes were analyzed. Hemorrhagic transformation was comfirmed by CT scan or MRI within 7 days. The functional outcome was measured by modified Barthel Index and modified Rankin Scale (mRS) at 7 days and 90 days. Patients with lower albumin had significantly higher risk of HT (15.3% vs. 4.2%, P = 0.002) and sICH (6.2% vs. 1.4%, P = 0.03) than those with normal level of albumin. In univariate analysis for HT, atrial fibrillation and level of albumin were identified as significant factors (P < 0.001, P = 0.001 respectively). On multivariate logistic regression analysis, serum albumin level remained independent predictor of HT (OR = 4.369, 95% CI = 1.626-11.742, P = 0.003). No significantly difference were found in the clinical outcome at 7 days and 90 days between two groups (P > 0.05). Low level of serum albumin within 24 hours may be an independent predictor of post-thrombolytic HT.