Klebsiella pneumoniae is one of the leading causes of hospital outbreaks worldwide, mainly in hospitalized or immune-compromised individuals. Also, this could be due to the emergence of Multidrug resistance (MDR) Extended Spectrum Beta Lactamase (ESBL) and carbapenemase-producing strains. This study's main goals were to evaluate the prevalence of resistance demonstrated by K. pneumoniae strains found in clinical samples from Benghazi Medical Center and AL-jalaa Hospital and to find evidence of ESBL strains and their resistance to certain antibiotic. During the study period, K. pneumoniae was isolated from 320 clinical samples (urine, sputum, blood and wound). The procedure for processing of samples, identification, susceptibility toward antimicrobials and evidence of ESBL, MBL strains were carried out according to the recommended standards. PCR was used to detect β-Lactamase and carbapenemase resistance genes. From a total K. pneumoniae isolates, 120 (37.5%) were isolated from hospital patients. The isolates exhibited high resistance to all used antibiotics. Forty-eight (40%) of the isolates were ESBL producers. MDR and XDR were identified in 89% and 56% of isolates respectively. ESBL-CTX-M-15 gene and OXA-48 were detected in all isolates. Moreover, SHV and NDM were identified in four isolates. In this study shows the high rate of MDR in clinical K. pneumoniae isolates in hospitals. There is an urgent need to implement an antibiotic resistance surveillance system to regulate and continuously monitor the emergence of antimicrobial resistance.