To study the dynamic changes in peripheral blood levels of hypoxia inducible factor-1α (HIF-1α), vascular endothelial growth factor (VEGF), and Bcl-2 in patients with acute ischemic stroke (AIS) and its correlation to early neurological deterioration (END). Methods: We included 173 AIS patients in our study. Patients were divided into the END group (n=59) and non-END group (n=114) according to the NIHSS scores. The serum levels of HIF-1α, VEGF, and Bcl-2 in the peripheral blood of all patients were detected by ELISA at 12 h, 24 h, 3 d, 5 d, 7 d, and 10 d after hospitalization, and the relationship with END was evaluated. Results: The ratio of patients with NIHSS and DWI-ASPECTS scores ≤7 was higher in the END group than those in the non-END group (P<0.05). The serum levels of HIF-1α, VEGF, and Bcl-2 in AIS patients peaked at 24 h after hospitalization. Furthermore, the serum levels of HIF-1α, VEGF, and Bcl-2 in END patients were higher than those in non-END patients (P<0.05). Patients with more severe END showed higher serum levels of HIF-1 α, VEGF, and Bcl-2 (P<0.05). Multivariate logistic regression analysis showed that the incidence of END was positively correlated with HIF-1α, VEGF, and Bcl-2 (P<0.05). Conclusion: Peripheral blood levels of HIF-1α, VEGF, and Bcl-2 may serve as predictors of the degree of neurological deterioration after AIS.