Objective To investigate the clinical efficacy and prognostic factors of acute cerebral infraction (ACI) patients treated by intravenous thrombolytic therapy with alteplase (rtPA). Methods The clinical data of 120 ACI patients treated in our hospital from April 2015 to August 2017 were retrospectively analyzed and patients were divided into two groups, according to different treatment methods. The control group received the intravenous thrombolytic therapy. Based on the treatment of control group, the observation group received the intravenous injection and drip of 09mg/kg (≦50 mg) rtpA within 1h. The NIHSS and Barthel score were recorded. Then the clinical efficacy, adverse reactions and prognostic factors of the two groups were recorded and analyzed. Results The NIHSS score of the two groups at the same time point had significant difference (P＜0.05), which were gradually decreased with the treatment time prolonged. The BI score had no difference before treatment (P＞0.05), and they were higher in the observation group than in the control group after treatment at the same time point (P＜005). The total effective rate in the observation group was significantly higher than that in the control group (9833% vs 8333%;X2=8.107, P=0.004). The incidence of adverse reactions in the observation group was not significantly different from that of the control group (500% vs 333%;X2=0.209, P=0.648). Univariate analysis showed age, pretreatment NIHSS scores, heart disease, diabetes, nutritional status and others were prognostic factors (P＜0.05). Logistic multivariate regression analysis showed that NIHSS scores, history of heart disease and diabetes, nutritional status, and treatment modalities were all independent risk factors affecting the prognosis of patients (P＜0.05). Conclusion The intravenous thrombolytic therapy with rtPA can effectively and safely guarantee the prognosis for ACI patients, and the prognosis of patients is related to the severity, age, diabetes, heart disease and nutritional status.