The use of phage therapy as an alternative method of treating infections caused by multidrug-resistant bacteria has been a controversial issue. The present study sought to determine safety and therapeutic efficacy of environmentally obtained Staphylococcus aureus lytic phage against multidrug-resistant S.aureus (MDRSA) in mice. Phages and MDRSA were isolated from sewage and waste water collected from within Nairobi County. The isolated S.aureus bacterium was screened for resistance towards; Ceftazidime, Oxacillin, Vancomycin, Netilmicin, Gentamicin and Erythromycin, Trimethroprim-Sulfamethoxazole and Cefuroxime. Thirty BALB/c mice were randomly assigned into three groups; the MDRSA infection group (n=20), the phage-infection group (n=5) and non-infection group (n=5). After 24 or 72 hours post-infection (p.i.) with MDRSA, the infected mice were either treated with a single dose of clindamycin (8mg/kg/bwt) or 108 PFU/ml of S.aureus phage or a combination (clindamycin and S.aureus phage). Safety was determined by monitoring animal physical health post-infection as well as gross pathology and histopathology. Bacteremia was determined daily for 10 days and used to establish therapeutic efficacy of the phage. Treatment with phage was efficacious (100%) compared to clindamycin (62.25%) at 24hrs p.i and 87.5% at 72hrs p.i.) while combination therapy (75% at 24hrs p.i. and 100% at 72hrs p.i.). Efficacy of the treatment regimens was dependent on the time of treatment post infection. The mice infected with MDRSA and treated with phage had no bacteremia at day 7 post-treatment compared to those treated with clindamycin and combination therapy (P < 0.001). There were no tissue abscesses, inflammation in the brain, lungs and liver tissues of phage treated mice compared to those treated with clindamycin and combination therapy. The S.aureus phage obtained from sewage and waste water from within Nairobi County was safe and possessed therapeutic efficacy against MDRSA bacterium.