The etiological diagnosis of peripheral pulmonary infectious lesions (PPILs) is challenging due to the limitations of conventional microbiological methods (CMMs). This study aimed to evaluate the diagnostic value of metagenomic next-generation sequencing (mNGS) performed on bronchoalveolar lavage fluid (BALF) obtained via radial endobronchial ultrasound (r-EBUS) for PPILs. This single-center, retrospective diagnostic accuracy study enrolled 110 patients with PPILs who underwent r-EBUSguided BALF between January 2023 and December 2024. BALF samples were subjected to both mNGS and CMMs. The final diagnosis was established by two senior pulmonologists based on a comprehensive review of all clinical data. The diagnostic performance of mNGS and CMMs was compared against this final diagnosis. A definitive diagnosis was established in all 110 patients, with 68 cases identified as infectious lesions and 42 as non-infectious. The sensitivity of mNGS for detecting pathogens in infectious lesions was significantly higher than that of CMMs (89.7% vs. 47.1%, P < 0.001). The overall diagnostic accuracy of mNGS was also superior to CMMs (90.9% vs. 66.4%, P < 0.001). Among patients with positive mNGS results, clinical management was altered in 73.8% of cases based on the findings. mNGS uniquely identified pathogens in 31 cases that were missed by CMMs. For patients with PPILs, mNGS analysis of BALF samples obtained via r-EBUS demonstrates significantly greater diagnostic sensitivity and accuracy than conventional methods. This approach has a substantial impact on clinical decision-making, facilitating targeted antimicrobial therapy and representing a powerful tool in the diagnostic workflow for peripheral pulmonary infections. Kulcsszavak: metagenomic next-generation sequencing, peripheral pulmonary infectious lesions, radial endobronchial ultrasound, bronchoalveolar lavage fluid, etiological diagnosis