Objective To explore the distribution characteristics and drug resistance of pathogens in patients with acquired immunodeficiency syndrome (AIDS). Methods Clinical data of AIDS patients in a hospital from 2017 to 2021 were collected retrospectively, distribution and drug resistance of infectious pathogens as well as distributional difference between healthcare-associated infection (HAI) and community-associated infection (CAI) were analyzed. Results A total of 1 711 pathogenic strains were isolated from 3 677 AIDS patients, out of which CAI-, HAI- and colonized strain numbers were 1 523, 77, and 111. Pathogenic constituents of 3 groups were significantly different (P < 0.001), with Fungi as the major pathogens, accounting for 64.35%, 36.36%, and 50.45% respectively. Respiratory tract infection (RTI) was the major CAI (40.97%), and bloodstream infection (BSI) was the major HAI (28.57%), with a statistically significant difference in the constituent ratio of infection sites between CAI and HAI (P < 0.001). In RTI, BSI and urinary tract infection of AIDS patients, difference in constituent ratio of pathogens between CAI and HAI was statistically different (P < 0.05).Isolation rate of multidrug-resistant organisms among different strains was statistically different (P < 0.001). Isolation rate was the highest in methicillin-resistant Staphy-lococcus epidermidis (58.33%), followed by carbapenem-resistant Acinetobacter baumannii (44.44%), methicillin-resistant Staphylococcus haemolyticus (33.33%) and methicillin-resistant Staphylococcus aureus (33.33%). Conclusion There are obvious differences in the pathogenic constitutions in CAI, HAI and colonization of AIDS patients, as well as in the distribution of infection sites between HAI and CAI. Detection rates of multidrug-resistant organisms of different strains are varied, resistance rate to commonly used antimicrobial agents is high. To prevent the spread of MDROs in community, emphasis should be put on monitoring the dynamics of pathogen drug resis-tance in AIDS patients and rational usage of antimicrobial agents.