This randomized clinical trial aimed to assess the efficacy of argatroban in patients with acute ischemic stroke (AIS) who experienced early neurological deterioration (END). The study was conducted from April 4, 2020, to July 31, 2022, and included 628 patients, with a final follow-up on October 31, 2022. Patients were randomly assigned to receive either argatroban plus standard antiplatelet therapy or standard antiplatelet therapy alone within 48 hours of symptom onset. The primary outcome was good functional outcome at 90 days, defined as a modified Rankin Scale score of 0 to 3. The results showed that the argatroban group had a significantly higher proportion of patients with good functional outcomes (80.5% vs 73.3%), with a risk difference of 7.2% (95% CI, 0.6%-14.0%; P = .04). There was no significant difference in the rate of symptomatic intracranial hemorrhage between the two groups (0.9% vs 0.7%). The study concluded that argatroban, combined with antiplatelet therapy, significantly improved functional outcomes in patients with AIS and END.This randomized clinical trial aimed to assess the efficacy of argatroban in patients with acute ischemic stroke (AIS) who experienced early neurological deterioration (END). The study was conducted from April 4, 2020, to July 31, 2022, and included 628 patients, with a final follow-up on October 31, 2022. Patients were randomly assigned to receive either argatroban plus standard antiplatelet therapy or standard antiplatelet therapy alone within 48 hours of symptom onset. The primary outcome was good functional outcome at 90 days, defined as a modified Rankin Scale score of 0 to 3. The results showed that the argatroban group had a significantly higher proportion of patients with good functional outcomes (80.5% vs 73.3%), with a risk difference of 7.2% (95% CI, 0.6%-14.0%; P = .04). There was no significant difference in the rate of symptomatic intracranial hemorrhage between the two groups (0.9% vs 0.7%). The study concluded that argatroban, combined with antiplatelet therapy, significantly improved functional outcomes in patients with AIS and END.