Background: Botulinum toxin (BTX) presents a promising avenue for preventing arterial spasm and post-anastomotic thrombosis (PAT), significant complications following vascular surgery. Arterial spasm, characterized by involuntary constriction of arterial smooth muscle, impairs blood flow and can lead to ischemia and organ damage. PAT, the formation of a thrombus at the site of a vascular anastomosis, results in occlusion and potentially limb loss or death. Both complications share a common pathophysiological link: excessive smooth muscle contraction and platelet activation. BTX, a neurotoxin that inhibits acetylcholine release at neuromuscular junctions, effectively paralyzes smooth muscle by preventing its contraction. Preclinical studies demonstrate BTX's efficacy in reducing arterial spasm in various animal models by inhibiting vasoconstriction. Its application directly to the anastomotic site or regionally to surrounding tissues can prevent the spasm-induced reduction in blood flow crucial for successful healing. Moreover, BTX's impact extends beyond direct muscle paralysis. It modulates the inflammatory response, mitigating the release of pro-thrombotic factors and reducing platelet aggregation, thereby indirectly inhibiting PAT formation. The potential benefits of BTX extend to its ease of administration and localized effects, minimizing systemic side effects often associated with other antispasmodic agents. However, further research is crucial to optimize BTX's dosage, delivery method (e.g., direct injection versus regional block), and timing of administration for optimal efficacy. Large-scale clinical trials are needed to confirm its safety and efficacy in preventing arterial spasm and PAT in humans, particularly comparing its outcomes against established preventative strategies. Despite these necessary steps, BTX offers a novel and potentially transformative approach to improving outcomes in vascular surgery by mitigating these devastating complications. The targeted inhibition of smooth muscle contraction and its anti-inflammatory effects provide a compelling rationale for continued investigation into BTX as a preventative measure.