This study aimed to explore the impact of unexpected early termination during intravenous thrombolysis on clinical prognosis in patients with acute ischemic stroke (AIS). Patients who received intravenous thrombolysis were divided into an early termination group and a normal treatment group. The causes of unexpected termination were analyzed, and the prognosis was compared between the groups. The main causes of early termination of thrombolytic therapy included subjective wishes of family members (11.8%, 4) and persistently elevated blood pressure (14.7%, 5). The effective rate of thrombolytic therapy in the early termination group was significantly lower than that in the normal treatment group (P < 0.05). The rate of early neurological deterioration in the early termination group was significantly higher than that in the normal treatment group (P < 0.05). There was no significant difference in the incidence of symptomatic intracranial hemorrhage after thrombolysis between the two groups (P > 0.05). The average mRS score of the early termination group was significantly higher than that of the normal treatment group (P < 0.05). Multivariate analysis indicated that early termination of thrombolytic therapy and cumulative dosage of rt-PA before termination were the main factors affecting the 3-month prognosis. Subjective wishes of family members and persistently elevated blood pressure may be the main causes of early termination of thrombolysis, and the 3-month prognosis of patients could be adversely affected by early termination of thrombolytic therapy and cumulative dosage of rt-PA. Certain measures, such as popularizing thrombolytic health education and optimizing blood pressure management before and during thrombolysis, may be helpful for the normal operation of intravenous thrombolysis.