Background: Klebsiella pneumoniae is an important cause of healthcare-associated infection. Carbapenemases have increasingly been reported in Enterobacteriaceae, especially in K. pneumoniae. Propose: The objective of this study was to determine antibiotic resistance patterns, and the molecular epidemiology of multidrug resistant K. pneumoniae isolates, obtained from hospitalized patients in Shiraz, Iran. Methods: In this study, 60 K. pneumoniaeisolates were collected from Nemazee and Faghihi referral hospitals. Antibiotic susceptibility testing and MIC were performed by disk diffusion test and Epsilometer (E)-test strips, respectively. Carbapenemase genes were identified by polymerase chain reaction and sequencing. Then, clonal relationships were analyzed, using PFGE. Results: Thirty-three out of 60 K. pneumoniae isolates were resistant to carbapenems. Among the isolates, 86.6% were multidrug resistant (MDR). Polymyxin B (18.3%) and tigecycline (23.3%) were shown to be the most active agents against K. pneumoniae isolates. In our study, the high prevalence of bla NDM (45%) and bla OXA-48 (10%) was detected. Conclusion: The results of this study revealed the widespread carbapenemase gene between different wards in hospitals as a risk factor for treatment options. PFGE analysis showed 11 clusters and 3 singletons based on an 80% similarity level. Also, PFGE analysis showed that there were similar genetic patterns among K. pneumoniae isolates and these patterns were responsible for the distribution of infection in hospitals.