The aim of this study was to investigate the prevalence of carbapenem-resistant Klebsiella pneumoniae (CRKP) and the most common types of carbapenemases, metallo-beta-lactamases (MBLs), and extended-spectrum beta-lactamases (ESBLs) among CRKP isolates in a tertiary hospital in Isfahan, Iran. Eighty non-repetitive clinical isolates of K. pneumoniae were obtained from different clinical specimens. Antibiotic resistance pattern of isolates was determined by disk diffusion method and production of carbapenemases and MBLs was confirmed using modified Hodge test and E-test, respectively. Molecular detection of the antibiotic resistance genes was performed using PCR. Fifty-one (63.8%) isolates have decreased susceptibility to carbapenems, of which 46 (90.2%) isolates were as carbapenemase producer and four (7.8%) isolates were positive for MBLs, phenotypically. The results of PCR showed that the prevalence of bla, bla, bla, bla, and bla genes among CRKP isolates were 90.2%, 15.7%, 98%, 96.1%, and 90.2%, respectively. No isolates carrying the bla, bla, bla, bla, and bla genes were detected. This study showed that the production of OXA-48 is one of the main mechanisms of resistance to carbapenems in CRKP isolates in Isfahan. In addition, the dissemination of NDM-producing CRKP isolates is a potential risk for the health care system of this area in the near future.