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Background: Nosocomial infections (NIs) are an important public health problem worldwide, particularity in the intensive care units (ICUs). Objectives: The current study aimed to detect and highlight NIs as the critical factor in increasing mortality and morbidity to clarify the current health priorities and challenges in Iran. Patients and Methods: It was a retrospective study on 376 selected patients admitted in ICU at a public hospital in Tehran, Iran, from 2012 to 2014. The major studied NIs included: ventilator associated pneumonia (VAP), central venous catheter related primary bloodstream infections (CRBSIs or BSI), surgical site infections (SSIs) and catheter associated urinary tract infections (CAUTI or UTI). NIs were defined based on the centers for disease control and prevention (CDC) definitions. Site specific NIs rates, mortality rate and the length of hospital stay and other demographic or clinical variables were extracted. Results: Three hundred-four patients were examined for NIs. NIs rate was 19.7% and mortality rates were 44.4% and 21.72% in infected and uninfected patients, respectively. The most frequent NIs was VAP and the highest observed rates of mortality were BSI in males (P = 0.050) and UTI in females (P = 0.05). The mortality rate in the infected patients was twice the other patients [2.187 (CI: %95: 1.154.13), P = 0.010]. The results showed that patients with cardiovascular respiratory dysfunction were exposed to higher risk of death. Infection rate increased in patients with diabetes and endocrine disease. Conclusions: To manage ICU patients, risk factors and causative procedures contributing to incidence and development of Nis should be considered. The most considerable points are accurate disinfection and more strict infection control procedure especially for prevent of VAP and BSI, which associated with the increasing of patient's mortality. This issue is more crucial in the cases of the cardiovascular respiratory and diabetic patients.