ObjectiveTo evaluate the localization accuracy and perioperative safety of three-dimensional (3D)-printed guide plate localization based on digital lung models in minimally invasive surgery for pulmonary nodules, and to provide an optimized strategy for precise localization of early-stage lung cancer. MethodsPatients with pulmonary nodules who underwent minimally invasive sublobar resection between January 2025 and January 2026 were enrolled. They were randomly allocated to a CT-guided group, a territory analysis group, and an intelligent guide plate group in a 1:1:1 ratio using a computer-generated random sequence. The intelligent guide plate group utilized dual-phase CT data to construct individualized digital lung models and design 3D-printed puncture guide plates for preoperative localization. The three groups were then compared in terms of localization accuracy (evaluated by 3D spatial linear distance grading for the CT-guided and intelligent guide plate groups, and by resection margin distance concordance grading for the territory analysis group), perioperative indicators, and complications. ResultsA total of 75 patients were enrolled, including 26 males and 49 females, with a median age of 56 years (range, 24-81 years). There were 26 patients in the CT-guided group, 26 in the territory analysis group, and 23 in the intelligent guide plate group. The high-precision rate was 60.87% (14/23) in the intelligent guide plate group and 61.54% (16/26) in the CT-guided group, with no statistically significant difference (P=0.944). In the territory analysis group, the resection margin distance concordance was graded as high in 17 patients (65.38%), moderate in 6 (23.08%), low in 2 (7.69%), and absent in 1 (3.85%). Defining high/moderate precision for the CT-guided and intelligent guide plate groups and high/moderate concordance for the territory analysis group as the ideal localization criteria, the qualification rates were 92.31% (24/26), 91.30% (21/23), and 88.46% (23/26), respectively, with no statistically significant difference among the three groups (P=0.886). There were no statistically significant differences in operative time, blood loss, drainage volume, pain score, or postoperative hospitalization costs among the three groups (all P>0.05). The overall complication rate also did not differ significantly among the three groups (P=0.847), and the complications were predominantly mild, including pulmonary air leakage, intermuscular venous thrombosis, pulmonary infection, hepatic insufficiency, etc. All patients improved after symptomatic treatment, with no severe complications encountered. After a median follow-up of 7 months, there were no patients of recurrence, metastasis, or death. Conclusion3D-printed guide plate localization based on digital lung models can effectively restore pulmonary physiological motion and eliminate the "displacement error" of traditional guide plates. It is comparable to CT-guided and territory analysis localization in terms of accuracy and safety, representing a safe and feasible novel precise localization strategy for minimally invasive surgery of early-stage lung cancer.