Antimicrobial-resistant Klebsiella pneumoniae(K. pneumoniae) constitute a major global health warning and is significantly implicated in severe infections associated with increased morbidity and mortality. As hospitalized patients in the ICU are more vulnerable to severe infections with increased cost of treatment and prolonged hospital stays, we aimed to compare antimicrobial susceptibility of K. pneumoniae obtained from intensive care unit (ICU) and non-intensive care unit (non-ICU) patients as well as to investigate potential impact of antimicrobial resistance on patient outcome. A retrospective, cross-sectional study conducted on ICU and non-ICU patients having K. pneumoniae infection during 2021 at Prince Mohammed bin Abdulaziz Hospital (PMAH) in Riyadh. Data regarding K. pneumoniae and their antimicrobial susceptibility, were retrieved and analyzed through R Software. 229 K. pneumoniae were isolated, 33.2% from ICU patients, and 66.8% from other departments. Most of the patients were males (66.8%) belonged to the older age group (62.9%). The isolates were obtained from endotracheal aspirate, sputum, blood, urine and wound samples. The ICU patients developed higher resistance to all examined antibiotics than non-ICU (p<0.001). More than 60% of ICU Klebsiella isolates were extended-spectrum b-lactamases (ESBL) and multidrug resistant (MDR) compared to non-ICU isolates (p<0.001). The most effective drugs were amikacin, imipenem, and meropenem, but their effectiveness substantially decreased against MDR strains. There was a statistically significant difference between the MDR, ESBL, and sensitive groups regarding hospital stay and mortality (P< 0.001). ICUs have exhibited a remarkable increase in MDR K. pneumoniae, which has a negative impact on patient outcomes.