Objective To analyze the clinical data of patients with Tropheryma whipplei pneumonia, and summarize the clinical characteristics, diagnosis, and treatment methods of Tropheryma whipplei pneumonia. Methods The data of Tropheryma whipplei pneumonia patients from three hospitals in Hunan Province between January 1, 2021 and October 1, 2022 were retrospectively collected. The clinical symptoms, laboratory examination, metagenomics next-generation sequencing (mNGS), CT imaging features, diagnosis and treatments of the included patients were analyzed. Results A total of 4 patients were included. Among them, there were 2 males and 2 females. The main manifestations were cough, expectoration, fever, and shortness of breath. There were 2 cases of diffuse ground glass opacity in both lungs, 1 case of pulmonary nodule, 1 case of pulmonary cavity, 1 case of pleural disease, 2 cases of pulmonary exudative lesions, and 1 case of mediastinal lymphadenectasis. The mNGS results showed that Tropheryma whipplei was detected in all 4 patients, and the median number of serial number (lower quartile, upper quartile) was 1 528 (1 480, 1 576). After anti infection treatment, 3 cases were treated effectively, and 1 case had poor treatment effect. Conclusions mNGS is an effective method to diagnose Tropheryma whipplei pneumonia. The measurement of serum lactate dehydrogenase level is helpful to evaluate the disease and determine the prognosis. Piperacillin tazobactam, meropenem and doxycycline are effective for this disease, while moxifloxacin and trimethoprim / sulfamethoxazole are not recommended because they may be naturally resistant. Without active etiological treatment, the disease may persist in migration and lead to extrapulmonary involvement.