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Background and Objectives: The frequency of multidrug-resistant Klebsiella pneumoniae (MDRKP) has dramatically increased worldwide in recent decades, posing an urgent threat to public health. The aim of this study was to assess the extent of K. pneumoniae in the Aseer region and explore the corresponding antimicrobial resistance profile over the last ten years. Materials and Methods: A record-based retrospective study was conducted in a tertiary hospital during the period of 2013 to 2022. The study targeted laboratory samples taken from patients admitted to the hospital and sent for K. pneumoniae culturing. We included only samples taken from the patient and confirmed by the lab. Data were extracted using a pre-structured data extraction sheet to avoid data-collection bias and confirm the inter-rater precision. Statistical Package for Social Sciences (SPSS) version 26 was employed for statistical analysis. All relationships were tested using Pearson X 2 test for categorical data or chi-square for linear trend for resistance rate over years. Results : We obtained 3921 samples of isolated K. pneumoniae out of 28,420 bacterial samples. The isolation rate began at 11.3% in 2013, decreased to 6.1% in 2016, and then increased to a peak of 16.3% in 2021, before slightly decreasing to 12.8% in 2022. In total, 23.7% of K. pneumoniae samples were identified in urine samples, 19% in sputum samples, 14% in wound samples, and 11.7% in blood samples. The overall antibiotic resistance rate of K. pneumoniae from 2013 to 2022 showed a significant increase, particularly during 2020 and 2021, before decreasing again in 2022. The resistance rate decreased from 22.2% in 2013 to 18.6% in 2016 and increased to 54.6% and 56.4% during 2020 and 2021, respectively ( p = 0.039) . Conclusions: We observed a significant shift in K. pneumoniae resistance for some antibiotics during the study period, highlighting the urgent need for enhanced antimicrobial stewardship and infection-control measures.