BACKGROUND Post-infectious organizing pneumonia (OP) is a rare clinical entity associated with nonspecific clinical features and can be easily misdiagnosed. This study aimed to investigate the clinical feature differences between cryptogenic organizing pneumonia (COP) and post-infectious OP. METHODS We retrospectively analyzed clinical data on demographic characteristics, clinical manifestations, laboratory findings, radiological findings, treatments, outcomes, and prognosis of 31 cases of COP and 26 cases of post-infectious OP. Patients were treated in Beijing Chao-yang Hospital between July 2005 and January 2013. RESULTS Compared with patients with COP, patients with post-infectious OP are more prone to show fever (88.5% vs. 38.7%, p < 0.05) and crackles (46.2% vs. 6.5%, p < 0.05). The elevation of PCT serum levels is more obvious in the early stage of post-infectious OP (5.24 ± 1.96 vs. 0.28 ± 0.09) and bilateral lung consolidations and patchy shadows are the most common radiological findings (70.2%). Pathogens are more prone to be confirmed within 48 hours after admission and the diagnosis time is longer (10.0 ± 0.8 vs. 7.2 ± 0.4 days). The incidence of mechanical ventilation (50% vs. 19.4%) and the utilization rate of antibiotics are higher (100.0% vs. 70.9%). The dosage (0.58 ± 0.04 vs. 0.78 ± 0.04 mg) and utilization time of glucocorticoids (5.7 ± 0.4 vs. 7.9 ± 0.8 months) are obviously reduced. CONCLUSIONS The morbidity of post-infectious OP is not uncommon. PCT serum level is helpful in the diagnosis and differential diagnosis, but invasive procedures like bronchoscopic or surgical lung biopsy are the golden-standard methods to confirm diagnosis. Similar to COP, antibiotics are effective in the early stage of post-infectious OP, but glucocorticoids are effective in the late stage. The prognosis of post-infectious OP is good.