Introduction: Pseudomonas aeruginosa has been a major nosocomial pathogen associated with nosocomial pneumonia, surgical site infections and UTI in patients admitted to intensive care units in the recent past(1). Major risk factors includes prolonged hospitalization, ventilation, underlying immunocompromised state and inadequate or irrational antimicrobial therapy(2). Despite improvements in therapy due to introduction of newer antimicrobials, P. aeruginosa is intrinsically resistant to number of antimicrobials, they aroused a major challenge to overcome the morbidity and mortality caused by multidrug and pan drug resistant P. aeruginosa(3). Drug resistance in turn leads to prolonged hospital stay and increased expenditure, which causes increased cross infections and poorer clinical outcomes. The present study investigated the prevalence of resistance mechanisms among Multi Drug Resistant Pseudomonas aeruginosa (MDRPA) clinical isolates from a tertiary care hospital. Methods: Seventy-five MDRP. aeruginosa isolates were obtained from 226 patients admitted in various wards. Antimicrobial susceptibility testing was performed by disk diffusion method and all these isolates were found to be MDR. All the isolates were subjected to different phenotypic assays to detect the production of enzymes such as ESBL, AmpC and MBL,. MIC determination was done by agar dilution method for Meropenem and Polymyxin B. Further, quantitative evaluation of biofilm production by was carried out by microtitre plate assay, since many studies have shown positive correlation between MDR and biofilm formation. Results: Of the 75 MDR P. aeruginosa, 36% were resistant to imipenem and 80% to meropenem. All the isolates were sensitive to polymyxin B. MBL production (38.67%) was found to be the predominant resistance mechanism followed by ESBL production (26.67%). None of them showed AmpC production. Ninety three percent (93%) of the strains produced abundant biofilms. Conclusion: P. aeruginosa was shown to be predominant nosocomial pathogen showing resistance to most of the available antibiotics including carbapenems. MBL is shown to be predominant mechanism for development of resistance in the present study.