Objective To improve the knowledge and diagnostic accuracy of combined pulmonary fibrosis and emphysema (CPFE) syndrome in connective tissue diseases (CTD) by summarizing the clinical characteristics of 20 CTD patients with CPFE and reviewing literatures. Methods The medical records of 20 CTD patients with CPFE from January 2011 to June 2015 were retrospectively analyzed. Results There were 11 males and 9 females. The average age was 47 years. Among them, 4 patients were smokers and 15 patients were nonsmokers. The average duration of CTD was 3.5 years with an average onset age of 41 years. Respiratory symptoms were reported in 17 patients and Velcro rale was found in 9 patients; The most common type of CTD disease in these 20 patients was inflammatory myopathy (9 patients, 45%) followed by systemic sclerosis (SSc) (4 patients, 20%). High resolution computerized tomography of lung showed typical radiological features of CPFE containing fibrosis lesions predominantly distributed in the subpleural (14 patients) and basal (18 patients) parts and emphysema mainly located in upper zones. Relatively normal results of lung volume and ventilation function, and markedly reduced carbon monoxide transfer capacity were observed. One patient was confirmed with pulmonary hypertension and 1 patient died from severe inflammation and acute respiratory distress syndrome. Conclusions The CPFE syndrome can be identified in CTD patients as an entity with male predominance, especially among patients with inflammatory myopathy and SSc. Higher risk of secondary pulmonary hypertension and acute lung injury in these patients may increase mortality. Early differentiation of CPFE from pure interstitial lung disease in CTD patients could be helpful in improving prognosis.