Objective To investigate the distribution and resistance of pathogens isolated from the lower respiratory tract of the elderly patients with acute exacerbation of combined pulmonary fibrosis and emphysema (CPFE). Methods Clinical data of 76 elderly patients with acute exacerbation of CPFE hospitalized in the Department of Respiratory and Critical Care Medicine of the Second Hospital Affiliated to Chongqing Medical University and the Respiratory Center of Chongqing Zhongshan Hospital from January 2013 to January 2014 were collected and analyzed in the study. The results of bacterial culture and antimicrobial susceptibility testing were analyzed. Results There were totally 88 strains of pathogens collected from the 76 cases, which were mainly Gram-negative bacteria and fungi. The top 6 pathogens were Acinetobacter baumannii (24 strains, 27.3%), Candida albicans (18 strains, 20.5%), Klebsiella pneumoniae (10 strains, 11.4%), Pseudomonas aeruginosa (8 strains, 9.1%), Stenotrophomonas maltophilia (6 strains, 6.8%), and Enterobacter cloacae (6 strains, 6.8%). There were 26 cases identified with mixed infection. Most of the obtained pathogens were multiple drug resistant to testing antibiotics. Conclusion For the elderly patients with acute exacerbation of CPFE, they are more prone to getting infections. So, we should distinguish the pathogens, and then give rational use of antibiotics and even glucocorticoid treatment if necessary.