Introduction: Ventilator-associated pneumonia (VAP) has been considered as a healthcare-associated infection with high mortality. Acinetobacter baumannii and Klebsiella pneumoniae are the common causes of VAPs around the world. Methodology: This research was a retrospective observational study in the intensive care unit (ICU) in a tertiary referral collegiate hospital in Tehran between March 2016 and May 2018. Patients who fulfilled VAP due to documented Multidrug Resistant Acinetobacter baumannii (MDR-AB) or Extended Spectrum Beta Lactamase-producing Klebsiella pneumoniae (ESBL-KP) criteria were enrolled. General demographic features, duration of hospital stay, antimicrobial treatment regimens, duration of ICU admission, the period of mechanical ventilation (MV) and 30-day mortality were documented and compared. Results: 210 patients were found with clinical, microbiological and radiological evidence of VAP. In total, 76 patients with MDR-AB and 76 patients with ESBL-KP infections were matched in the final analysis. Duration of hospitalization in the patients with MDR-AB was significantly more than that of patients infected with ESBL-KP (p-value: 0.045). Patients diagnosed with MDR-AB VAP had a 65.8% mortality rate compared to 42.1% in the ESBL-KP infection group (p = 0.003). Conclusions: Results of the present study demonstrated that VAPs caused by MDR-AB may be more hazardous than ESBL-KP VAPs because they could be accompanied by a longer hospitalization course and even a higher mortality.