Objective To study the bacteriologic profile and drug resistance of respiratory infection in children, and to provide a basis for etiological diagnosis and rational use of antimicrobial agents. Methods A retrospective analysis was performed for 15 047 children who attended the hospital due to respiratory infection from January 2016 to December 2018. Their sputum samples were collected, and the Phoenix-100 automatic microbial identification system was used for the identification and drug sensitivity analysis of the isolated pathogenic bacteria. Results Of all 17 174 sputum samples detected, there were 2 395 positive samples, with a positive rate of 13.95%; a total of 2 584 strains of pathogenic bacteria were isolated, among which there were 1 577 (61.03%) Gram-negative strains, 967 (37.42%) Gram-positive strains, and 40 (1.55%) fungal strains. The most common pathogen was Haemophilus influenzae (33.90%), followed by Streptococcus pneumoniae (33.55%), Moraxella catarrhalis (19.20%), and Staphylococcus aureus (3.64%). Among the 2 331 children with positive infection, 251 had mixed infection, most commonly with Haemophilus influenzae and Streptococcus pneumoniae. The detection rate of pathogenic bacteria was higher in winter and spring and lower in summer and autumn. There was a significant difference in the detection rate of pathogenic bacteria between different age groups (P < 0.05), with the highest detection rate in infants aged 1 month to <1 year. Streptococcus pneumoniae and Staphylococcus aureus had a sensitivity rate of 100% to vancomycin, linezolid, and teicoplanin, and Haemophilus influenzae had a lower sensitivity rate to ampicillin, compound sulfamethoxazole and cefuroxime and a higher sensitivity rate to other drugs. Conclusions Haemophilus influenzae, Streptococcus pneumoniae, and Moraxella catarrhalis are the main pathogenic bacteria of respiratory infection in children, and mixed infection is the most common type of infection. The detection rate of pathogenic bacteria varies across seasons and ages. Different pathogenic bacteria have different features of drug resistance, and antibiotics should be selected based on drug sensitivity results.