Background: Device-associated health care-associated infections (DA-HAI) are one of the significant threats to patient safety concerning increased morbidity and mortality, particularly in intensive care units (ICUs). Objectives: We aimed to assess device-associated infection (DAI) rates, microbiological profiles, and attributable mortality in ICUs from a large tertiary care hospital. Methodology: This retrospective surveillance study was done over a one-year period by applying the Centers for Disease Control and Prevention (CDC) and National Healthcare Safety Network (NHSN) case definitions for calculating ventilator-associated pneumonia (VAP), central line-associated bloodstream infection (CLABSI), and catheter-associated urinary tract infection. Results: A total of 2022 patients were hospitalized in ICUs and acquired 86 DAIs, with an overall rate of 4.4 DAIs per 1,000 device days. The most frequently recognized infection was VAP (55.8 %), followed by CAUTI (32.6%) then CLABSI (11.6%). The most commonly isolated organisms were Enterobacteriaceae (43%), followed by non-fermentative Gram-negative bacteria (41%) and Gram-positive cocci (12%). Multidrug resistance was identified in 80% of the isolates. The crude excess mortality for CLABSI (66.7%) was higher than VAP (45.4%) and CAUTI (19.5%). Conclusions: The high incidence rates of DA-HAIs together with the prevalence of antimicrobial resistance highlight the requirement to implement a comprehensive care-bundle approach program as well as an antimicrobial stewardship.