Multidrug resistant (MDR) P.aeruginosa had emerged in Egypt and seen mainly in nosocomial infections due to the selective pressure by overusage of antibiotics. This study was planned to delineate prevalence of MDR P.aeruginosa in nosocomial infection patients, and to screen for ESβLs producing P.aeruginosa with typing of P.aeruginosa isolates in Menofia University Hospitals (MUH), Egypt. Our study included 287 inpatients admitted to Menoufia University Hospital and having different nosocomial infections. Samples from medical staff and from hospital environment were collected. Antibiotyping of P. aeruginosa isolates were determined. MDR and ESBLs P. aeruginosa were detected. Plasmid DNA analysis and pyocin typing were done. In our study, a total of 57 P. aeruginosa strains were isolated. P. aeruginosa and its MDR phenoype accounted for 19 % and 9.5% respectively of nosocomial infections. MDR and ESβLs producer P. aeruginosa infections were commonly isolated from burn wound specimens followed by urinary tract, respiratory tract and wound infections. We detected high rates of MDR P. aeruginosa (52%) and of ESβLs producer strains (45.6%) and those ESBLs strains were all MDR. Amikacin and imipenem were the most effective drugs against P. aeruginosa. 23 different resistance patterns were identified, profiles from (1 -8) were prevalent. The most prevalent antibiotype (2) included 12 MDR isolates, 9 clinical and 3 environmental isolates having same patterns. 61.5% of ESβLs isolates harbor plasmids. Five groups could be demonstrated among our P. aeruginosa isolates. Each had the same antibiotype and plasmid profile. In conclusions, our results clarified that threats of MDR and ESBLs P. aeruginosa become of major concern in our hospital and implementation of infection control strategies are major concerns to avoid the spread of this threat. Eenvironmental sources may have a significant role in spread of MDR P. aeruginosa among hospitalized patients. Combination of Journal of Virology & Microbiology 2 simple typing methods as antibiotyping with plasmid profiling may be the cheapest and effective method for tracing source of infection.