The authors aimed to determine whether early changes in fibrinogen were associated with the efficacy of intravenous thrombolysis at 24 hours after alteplase infusion. The authors retrospectively reviewed a consecutive series of 56 patients with acute ischemic stroke treated with alteplase in the clinical database. The fibrinogen levels were monitored at the first and fourth hours after alteplase infusion. Additionally, the National Institutes of Health Stroke Scale (NIHSS) scores were recorded to define the short-term efficacy of intravenous thrombolysis before and 24 hours after alteplase infusion. The patients were distributed into amelioration, deterioration, and inefficiency groups according the short-term efficacy of intravenous thrombolysis. One-way ANOVA and post hoc analysis were used to compare the differences in the clinical characteristics among these groups. The relationships among changes in the fibrinogen levels, other potential risk factors, and NIHSS scores were examined using logistic regression analysis. Fifty-two patients (mean age, 65.71 ± 11.04 years; male, 57.7%) were finally enrolled in the study. The median NIHSS of these patients was 11 (range, 2-23), and the mean time from symptom onset to thrombolysis was 187.17 ± 67.53 minutes. The frequency of hypertension in the deterioration group was significantly higher than that in the inefficiency group (P = .01). Changes in the fibrinogen level were more significant in the amelioration group than in the other groups (P < .05). Logistic regression analysis revealed that changes in the fibrinogen levels between the first and fourth hours were positively associated with the short-term efficacy of alteplase infusion (odds ratio, 3.98; 95% confidence interval, 1.56-10.16; P = .004). Early changes in fibrinogen levels may be a potential predictor for the short-term efficacy of alteplase treatment in acute ischemic stroke. Additionally, these changes may be helpful for determining the short-term efficacy of alteplase treatment and early therapeutic strategies in clinical practice.