BACKGROUND: Ischemic stroke was a major cause of mortality and disability worldwide. Mechanical thrombectomy (MT) has improved acute ischemic stroke treatment by restoring blood flow in large vessel occlusions. Yet, reperfusion injury remains a challenge, necessitating adjunctive neuroprotective strategies to enhance recovery. N-butylphthalide (NBP), with its anti-inflammatory and antioxidative properties, may improve functional outcomes post-MT. METHODS: This retrospective study analyzed 120 ischemic stroke patients treated with MT at a single institution from December 2020 to December 2022. Patients were divided into a routine care group (n = 56) and an NBP treatment group (n = 64). Baseline characteristics, comorbidities, and biochemical profiles were assessed. Functional outcomes were measured by the modified Rankin Scale (mRS) at 90 days. Statistical analysis included correlation and logistic regression to identify factors influencing recovery. RESULTS: Among the NBP group, a significantly higher percentage achieved favorable mRS scores (0-2) compared to the routine care group (62.50% vs 37.50%, P = 0.006). Smoking (OR 0.320, P = 0.021), diabetes (OR 0.246, P = 0.022), and elevated hs-CRP levels (OR 0.407, P = 0.004) were identified as negative predictors of functional recovery. Conversely, NBP treatment significantly improved outcomes (OR 3.248, P = 0.008). CONCLUSION: The study supports the potential of NBP as an effective adjunctive therapy in improving recovery following MT in ischemic stroke patients. Modifiable factors such as smoking and diabetes, along with elevated hs-CRP, negatively influence outcomes, highlighting the importance of comprehensive management.