Objective To investigate the value and safety of different lung biopsy methods in the diagnosis of peripheral lung masses. Methods A total of 286 elderly patients with peripheral lung lesions diagnosed by radiology in our hospital from June 2019 to June 2021 were enrolled as the study subjects. According to the methods of lung biopsy, they were divided into transthoracic needle lung biopsy group (TNLB group, n=165) and transbronchial lung biopsy group (TBLB group, n=121). McNemar test was used to calculate the sensitivity, specificity, accuracy, positive predictive value and negative predictive value of TNLB and TBLB in the diagnosis of properties of peripheral lung masses by taking pathological examination and follow-up result as the "gold standard". SPSS statistics 19.0 was used for data analysis. Student′s t test or Chi-square test was used for intergroup comparison depending on different data type. Results For the 165 patients from the TNLB group, 51 cases had positive and 114 cases had negative results after TNLB, and 9 negative cases were confirmed to be malignant by follow-up and surgical pathology. Among 121 patients receiving TBLB, 23 cases got positive and 98 cases negative results, and among the negative cases, 16 cases were confirmed to be malignant by follow-up examination. The sensitivity, specificity, accuracy, positive predictive value and negative predictive value in the diagnosis of peripheral lung masses were 85.00%, 100.00%, 94.55%, 100.00% and 92.11% for TNLB, and 58.97%, 100.00%, 86.78%, 100.00% and 83.67% for TBLB. The biopsyaccuracy rate was significantly higher in TNLB than TBLB (94.55% vs 86.78%,P<0.05). TNLB had higher incidence rate of complications than TBLB (24.85% vs 11.57%, P<0.05). TBLB had obviously higher positive detection rate for lesions ≥4 cm in diameter than those with diameter <4 cm (24.69% vs 7.50%, P<0.05). With regard to lesions <4 cm in diameter, the positive detection rate of TNLB was higher than that of TBLB (26.67% vs 7.50%, P<0.05). Conclusion TLNB has the advantages of accurate localization and high biopsy accuracy rate, but has more postoperative complications. TBLB can be used as a preferred biopsy method to improve the safety of biopsy for the elderly patients with peripheral lung masses, who has poor lung tolerance but large lesion diameter and lesion close to the central airway.