Objective <p>This study aimed to explore the efficacy of fasudil in preventing and treating cerebral vasospasm after aneurysmal subarachnoid hemorrhage (aSAH).</p> Methods <p>Eighty patients with aSAH were enrolled and randomly assigned to either a control group or a combination group. Patients in the control group received nimodipine alone, while those in the combination group were treated with both nimodipine and fasudil. Outcome measures included the incidence of cerebral vasospasm, overall therapeutic efficacy, serum biomarkers (NF-κB, MMP-9, S100B, BDNF, and NSE), hepatic and renal function indicators (ALT, AST, Cr, and BUN), Montreal Cognitive Assessment (MoCA), Modified Barthel Index (MBI), and adverse events.</p> Results <p>After treatment, the combination group exhibited a significantly lower incidence of cerebral vasospasm and a higher total effective rate compared with the control group (<i>P &lt;</i> 0.05). Moreover, serum levels of NF-κB, MMP-9, S100B, and NSE were markedly reduced, while BDNF, MoCA, and MBI scores were significantly higher in the combination group than in the control group (<i>P</i> &lt; 0.05).No significant differences were observed between groups in the incidence of adverse reactions or in ALT, AST, Cr, and BUN levels (<i>P</i> &gt; 0.05).</p> Conclusion <p>Combined therapy with fasudil and nimodipine for aSAH enhances overall treatment efficacy, reduces serum NF-κB, MMP-9, S100B, and NSE levels, lowers the risk of cerebral vasospasm, and elevates serum BDNF as well as cognitive and functional recovery scores, while maintaining a favorable safety profile.</p> <p><i>Clinical trial registration number</i> ChiCTR2200001252. The date of registration is January 2023.</p>