Abstract: Background　Vascular crisis is a critical postoperative complication following free flap transplantation, posing a significant threat to flap survival. Despite its clinical significance, consensus on optimal perioperative pharmacological management remains lacking. Objective　To evaluate the impact of vasopressors, analgesics, anticoagulants, and vasodilators on the occurrence of vascular crisis following free flap transplantation. Methods　A retrospective analysis was conducted on patients who underwent free flap reconstruction for tissue defects at Chinese PLA General Hospital from January 1996 to December 2024. Confounding bias was adjusted by inverse probability of treatment weighting (IPTW), and the associations between four prophylactic agents and vascular crisis were assessed with Bonferroni-corrected multiple comparisons. Results　A total of 323 patients (194 males and 129 females, mean age of 47.2±15.8 years) were included. The overall incidence of postoperative vascular crisis was 16.1%, with complete flap necrosis occurring in 5.0% of cases. Following IPTW, covariate balance was achieved across all exposure - nonexposure comparisons (standardized mean difference SMD < 0.1 for all variables). Weighted logistic regression revealed no statistically significant association between vascular crisis and vasopressor use (OR=1.369, 95% CI: 0.746 - 2.505), analgesic use (OR=0.876, 95% CI: 0.447 - 1.659), anticoagulant use (OR=2.931, 95% CI: 0.941 - 13.470), or vasodilator use (OR=0.990, 95% CI: 0.504 - 2.003). Sensitivity analyses yielded consistent results, supporting the robustness of the primary findings. Conclusion　 Intraoperative vasopressors and postoperative analgesics, anticoagulants, and vasodilators show no impact on postoperative vascular crisis.