Objective To explore the clinical efficacy and safety of ultra-early intravenous thrombolytic therapy in the treatment of acute cerebral infarction. Methods A retrospective study was performed on 260 patients with acute cerebral infarction in the Department of Neurosurgery from January 2014 to April 2017. Their clinical data were collected and analyzed. According to ultra-early thrombolysis or not, they were divided into thrombolytic group and control group, 130 cases in each group. Thrombolytic group was treated with recombinant human tissue plasminogen activator within a therapeutic window of 4.5 h, and the control group was given with conventional anticoagulation and antihypertensive therapy. National Institutes of Health Stroke Scale (NIHSS) score, Barthel index, long term prognosis and coagulation function, including activated partial thromboplastin time (APTT), prothrombin time (PT), thrombin time (TT) and fibrinogen (FIB) at different time points after treatment were used to compare the efficacy of the 2 groups. SPSS statistics 16.0 was used for data processing. According to the data type, Students′t test or Chi-square test was used in the comparison between groups. Results After treatment for 24 h, the patients in the thrombolysis group had significantly longer APTT [(32.9±2.8) vs (30.1±3.0) s], PT [(13.7±1.6) vs (12.8±1.5) s] and TT [(17.3±1.0) vs (16.1±1.3) s] (all P<0.05), but obviously lower FIB level [(2.6±0.4) vs (2.9±0.6) g/L, P<0.05] when compared with those in the control group. Before treatment, there was no significant difference in NIHSS scores between the 2 groups (P>0.05), but the scores were notably lower in the thrombolysis group than the control group in 24 h, and 7,4 and 28 d after treatment (P<0.05). At 1,3, and 6 months after treatment, the Barthel index of patients in the thrombolysis group was significantly higher than that in the control group at the same time (P<0.05). After 6 months of treatment, the rate of good prognosis was significantly higher in the thrombolysis group than in the control group (76.15% vs 64.62%,P<0.05). In the thrombolysis group, there was 1 case of gingival bleeding, 2 cases of epistaxis, and 13 cases of subcu-taneous hemorrhage at the site of intravenous infusion, but no other serious adverse events occurred. Conclusion Ultra-early intravenous thrombolytic therapy can effectively improve the symptoms of neurological deficits in the patients with acute cerebral infarction, and is of great significance for long-term rehabilitation.