Background: Pseudomonas aeruginosa , a gram-negative pathogen is commonly associated with nosocomial infections. Infections caused by P. aeruginosa can range from superficial skin infections to fulminant sepsis. Antimicrobial resistance is an area of prime concern in pseudomonal infections. The objective of the study was to evaluate and analyse the antibiotic susceptibility pattern of P. aeruginosa at a tertiary care hospital in South India. Methods: The study was carried out at Kasturba Medical College and Hospital, Manipal, India from January 2011 to December 2011. Ten different types of specimens were collected from patients who were culture positive for Pseudomonas aeruginosa . Antibiotic susceptibility was confirmed by disk diffusion technique on Muller-Hinton medium and was performed according to the Clinical Laboratory Standard Institute (CLSI) guidelines. Results: Out of 200 samples of P. aeruginosa 69.5% and 30.5% were from male and female patients respectively. Majority of the specimen from which P. aeruginosa was isolated consisted of sputum, pus and urine. Among the antimicrobial drugs tested, organism was most sensitive to carbapenems (77.5%), piperacillin-tazobactam (77%) and cefoperazone-sulbactam (72%). Resistance rates were high for fluoroquinolones (FQs) (43.5%), gentamicin (40.5%), tobramycin (40.5%), ticarcillin-clavulanic acid (39%) and aztreonam (38%) when compared to cefepime (31.5%), ceftazidime (32.5%), netilmicin (34.5%) and amikacin (35%). Conclusions: Carbapenems and piperacillin-tazobactam were the best antipseudomonal agents with highest sensitivity to P. aeruginosa . FQs, gentamicin and tobramycin were the least effective drugs against P. aeruginosa as monotherapy.