Background: The increasing trend of multi-drug resistant Pseudomonas aeruginosa implicated in most nosocomial infections in Nigeria has necessitated this present study; which investigated the resistance and susceptibility patterns of P. aeruginosa isolated from hospitals in Onitsha, Southeast Nigeria. Methods: A total of 22 clinical and environmental isolates of P. aeruginosa were recovered from 10 hospitals in Onitsha, Southeastern Nigeria and they comprised 3 (13.6%) isolates from hospital sinks, 2 (9.1%) from hospital mops, patients' table, trolleys, sphygmomanometer, laboratory work bench and cleaning buckets respectively and 1 (4.5%) from theatre bed, wound swab, nasal swab, nurses' tray, floor, disinfectant and ear swab respectively. Antimicrobial susceptibility testing for 11 antibiotics was performed by agar disk diffusion on Muller-Hinton agar plates and multiple antibiotic resistance index (MARI) was also determined. Results: Antibiogram categorized the 22 P. aeruginosa isolates into 5 different antibiotypes. Results showed that each isolate was resistant to ≥ 3 classes of antibiotics; 3 (13.6%) were resistant to 7 antibiotics; 11 (50%) were resistant to 8 antibiotics; 5 (22.7%) were resistant to 9 antibiotics and 3 (13.6%) were resistant to 10 antibiotics. Susceptibility testing showed that all the 22 isolates were multi-drug resistant being resistant to at least 3 classes of anti-pseudomonal drugs. P. aeruginosa had highest resistance rates to the cephalosporins (ceftazidime, cefuroxime, cefotaxime, cefepime) at 100%, followed by piperacillin (100%), amoxicillin-clavulanic acid (100%) and tetracycline (100%). The multi-drug resistance (MDR) rate was determined at 100%. Highest number of susceptible isolates was recorded for imipenem (100%) and amikacin (86.4%) respectively. Conclusion: The high resistance profiles observed in this study could limit available therapeutic options for infections caused by these multidrug resistant strains if they are not properly detected and reported by hospital laboratories.