Background: The most frequent infection in ICUs, Ventilator-associated pneumonia (VAP); potentially life threatening, stands for another challenge in medicine. Earliness in diagnosis is pivotal. Constant surveillance is crucial to confront the issue by defining expedient strategies. Purpose: The study intended to present our experience in the intensive care units (ICUs) of causative organisms of VAP and their antimicrobial susceptibility profile, with the effect of different variables; utilising this data to devise more pertinent empirical therapy. Methodology: A prospective clinico-microbiological review of patients mechanically ventilated for ?48 hrs and in agreement with a clinical criteria, at a tertiary care set up, from multidisciplinary ICUs was undertaken by standard microbiological techniques. Antimicrobial resistance was patterned. Results: Occurrence of VAP was 49.07%. Late onset type (65.28%) was more frequent. Majority (85.95%) were caused by Gram Negative bacteria (GNB). Acinetobacter baumannii (30.58%) was most regular, followed by Pseudomonas aeruginosa (27.27%). 15 isolates (4 Escherichia coli, 9 Klebsiella spp., 2 Enterobacter spp.) produced ESBL (Extended Spectrum beta lactamase). 1 MRSA (Methicillin resistant Staphylococcus aureus) was isolated. Cases of OP (Organophosporous) poisoning- 31.48%; associated advancing age (__ampersandsigngt;60 years) - 45.28%, Diabetes mellitus - 26.39% and COPD - 22.68% were pre-eminent. Conclusions: Monitoring trends of drug profile of the causative agents is of cardinal benefit for restricting the use of empiric broad spectrum antimicrobials which predisposes to colonization. Constant evaluation of current practice on basis of antibiotic consumption patterns, timely availability of data and programs to reduce or alter antibiotic-prescribing practices is crucial to avert the terrible impact of antimicrobial resistance.