Objective: To analyze the clinical distribution and drug resistance trends of clinical isolates ofKlebsiella pneumoniaefrom a tertiary hospital in Henan Province from 2017 to 2021, and to provide recommendations for the rational use of antibiotics in the hospital. Methods: A retrospective study was conducted to collect and organize the drug sensitivity test results and clinical data of clinical isolates ofKlebsiella pneumoniaein the hospital from 2017 to 2021. The data was analyzed using WHO NET 5.6 and SPSS 26.0 software. Results: A total of 1 379 strains ofKlebsiella pneumoniaewere isolated in the hospital from 2017 to 2021, with an isolation rate of 17.87%. There was no significant difference in the isolation rates ofKlebsiella pneumoniaeover the entire five-year period.The top three sources of isolates were sputum(65.99%), secretion(12.98%), and urine(8.85%). The main departments for collecting isolates were the respiratory department(26.03%) and the ICU(24.58%), with the isolation rate in other departments being less than 5%. The drug sensitivity results showed that, except for the resistance rate of cefoperazone, the resistance rates of other antibacterial drugs showed statistically differences over the five years, generally showing a stable or decreasing trend. The carbapenem drugs imipenem and meropenem decreased from 33.1% and 33.5% in 2017 to 13.7% and 14.4% in 2021, respectively. In addition, the resistance rates of chloramphenicol and tetracycline class minocycline showed an increasing trend. Conclusion Klebsiella pneumoniaeis still the main pathogen isolated in the hospital, mainly in the respiratory department and ICU, with sputum, urine, and blood being the main specimens. The resistance rates have shown a stable or decreasing trend over the past five years, with a significant decrease in carbapenem resistance rates. However, attention should still be paid to the increasing resistance rates of chloramphenicol and minocycline. Clinically, antibiotics should be used rationally based on drug sensitivity results.