Surveillance of multi drug resistant organisms in a health care setting is a necessity to have optimum treatment out come and less of treatment failures. Once any health care setting gets colonized with multi drug resistant organisms, it is very difficult to decontaminate the environment. On review of our data, for 12 months of year 2008 the prevalence of difficult to treat organisms with poor clinical outcome especially in ICUs have been identified. The need for surveillance, prescription auditing & computer assisted retrieval of data has been emphasized and discussed in detail with respect to various high quality samples like blood, urine, respiratory, pus and sterile body fluids. The prevalence of MRSA & VRE has been documented 30 to 40% and 10%, respectively. Over all prevalence of penicillin intermediate resistant Streptococcus pneumoniae was found to be 9.52%. ESBL, AmpC, and Carbapenemase producing organisms were found to be 40 to 60%, 70 to 80% & 2 to 80% respectively in various multi drug resistant organisms like E. coli, Klebsiella spp., Pseudomonas spp. and Acinetobacter spp. 8% Pseudomonas spp. were found to be resistant to colistin in ICU samples. Enteric organisms were found to have high level ciprofloxacin resistant in 21.6% isolates, while S. paratyphi A isolation increased over a period of time. Yeast fungi isolated from blood predominantly were non-candida albicans (84.8%).