ObjectiveTo investigate the impact of the interval between neoadjuvant immunotherapy and surgery on the prognosis of patients with non-small cell lung cancer (NSCLC), and to provide evidence-based guidance for the selection of surgical timing in clinical practice. MethodsClinical data of NSCLC patients who underwent surgery following neoadjuvant immunotherapy at the First Hospital of Lanzhou University from October 2020 to May 2022 were retrospectively collected. According to the interval between the last neoadjuvant immunotherapy and surgery, patients were stratified into three groups using cutoff values of 4 and 6 weeks: a ≤4 weeks group, a >4-6 weeks group, and a >6 weeks group. The Kaplan-Meier method and Cox proportional hazards model were employed to analyze overall survival (OS) and recurrence-free survival (RFS), while logistic regression was performed to identify independent predictors of major pathologic response (MPR). ResultsA total of 165 patients were finally enrolled, comprising 143 (86.67%) males and 22 (13.33%) females, with a median age of 65.00 years. The ≤4 weeks, >4-6 weeks, and >6 weeks groups included 33, 80, and 52 patients, respectively, with well-balanced baseline characteristics among the groups. The median follow-up duration was 28.3 months with a follow-up rate of 89.2%. The overall MPR (including pathologic complete response) rate was 55.16%; however, no significant difference in pathological response was observed among the three groups. Kaplan-Meier analysis revealed no obvious separation in OS or RFS among the three groups. Nevertheless, when regrouped using a cutoff of 65 days, the ≤65 days group demonstrated significant survival benefits (OS: P=0.032; RFS: P=0.003). Logistic regression analysis identified squamous cell carcinoma as an independent predictor of MPR (P=0.05). Cox regression analysis showed that receiving ≥3 cycles of neoadjuvant therapy (P=0.01) and postoperative adjuvant therapy (P=0.02) were independent protective factors for OS. ConclusionThe interval between neoadjuvant immunotherapy and surgery of ≤4 weeks, >4-6 weeks, or >6 weeks has no significant effect on surgical safety, pathological response, or long-term prognosis in patients with NSCLC.