Objective To investigate the distribution and drug susceptibility profile of pathogens causing nosocomial infection in organ transplant patients, so as to provide a basis for clinical diagnosis and treatment. Methods The clinical samples were collected from 149 organ transplant patients in Changhai Hospital of Navy Medical University (Second Military Medical University) between Jan. 2016 and Dec. 2017. The isolates were identified using VITEK 2 Compact automatic microorganism analyzer system or Microflex matrix-assisted laser desorption ionization-time of flight mass spectrometry. The susceptibility test for bacteria was carried out by VITEK 2 Compact automatic microorganism analyzer system, and the susceptibility test for fungus was carried out by ATB Fungus 3 susceptibility kit. Results Most pathogenic specimens were derived from flushing fluid samples (42.3%, 101/239). A total of 239 strains of pathogens were isolated from 149 patients, including 135 (56.5%) of Gram-negative pathogens, 77 (32.2%) of Gram-positive pathogens, and 27 (11.3%) of fungi. Klebsiella pneumoniae was the most found Gram-negative pathogens (13.8%, 33/239), and its resistance to common antibiotics, such as piperacillin, was generally high with the resistance incidence being more than 50.0% and it had a tendency of multi-drug resistance. Escherichia coli had high sensitivity to carbapenems, with incidence of drug resistance being less than 5.0%. Acinetobacter baumannii had high resistance to carbapenems, with incidence of drug resistance being 81.0%. Among Gram-positive pathogens, Enterococcus had 40.0%-77.2% resistance incidence to penicillin and ampicillin, but was sensitive to linezolid and vancomycin. The sensitivity of fungi for most antifungal agents was higher than 80.0%, especially for voriconazole (96.3%). Conclusion Gram-negative pathogens are the primary pathogens causing nosocomial infection in organ transplant patients. Klebsiella pneumoniae is the main pathogen and has a tendency of multi-drug resistance. Gram-positive pathogens are susceptible to linezolid and vancomycin. Fungi are susceptible to commonly used antifungal agents.