Infections with extended-spectrum beta-lactamase (ESBL)-producing strains are seen at increasing rates, resulting in increased morbidity, mortality, length of hospitalization, and cost. Effective and safe treatment of these infections is important. The aim of this study was to compare the effectiveness of piperacillin-tazobactam (PTZ) and carbapenems in nosocomial infections with ESBL-producing Escherichia coli and Klebsiella pneumoniae in hospitalized patients. Materials and Methods: This study was performed retrospectively on patients who were infected with ESBL-producing E. coli and K. pneumoniae while hospitalized in Ankara Atatürk Tranining and Research Hospital between 2014 and 2017. Both PTZ-and carbapenem-susceptible isolates were included in the study. Patients with signs of infection who were older than 18 years, hospitalized for at least 48 hours, and received PTZ or carbapenem therapy were included in the study. Patients who received PTZ and carbapenem antibiotics consecutively in same infectious episode, received another antibiotic active against ESBL-producing microorganisms, received the selected antibiotic for less than 48 hours, or had polymicrobial infection were excluded from the study. Demographic characteristics, comorbid diseases, antibiotics used and their dose/duration, mechanical ventilation, presence of central catheter, clinical and microbiological responses to treatment, and end-of-treatment and 30-day mortality were recorded and compared. Results: Of the total 113 patients, 60 (53.1%) were male and the mean age was 66.14±18.2 years. Of the patients, 73.5% had E. coli and 26.5% had K. pneumoniae. Seventy patients (61.9%) received carbapenem and 43 patients (38.1%) received PTZ treatment. Microbiological eradication rate was 71.7% (43/60) in patients with control cultures. Clinical response was observed in 72.6% of the cases. The overall mortality rate was 31.0% (n=35). There were no significant differences between the groups in clinical and microbiological response (p=0.055; p=0.303) or end-of-treatment and 30day mortality (p=0.180, p=0.288). Age and bacteremia was found to be independent risk factors for mortality (p=0.006 for both). Conclusion: PTZ is an important alternative for infections caused by ESBL-producing microorganisms. In recent years, the need for rational antibiotic use has increased and carbapenem-sparing treatments have became more important. Piperacillin-tazobactam is one of the best alternatives and has comparable effectiveness in infections caused by ESBL-producing E. coli and Klebsiella spp.