Urinary tract infections (UTIs) remain the most common infections that affect all age groups worldwide. This study was aimed at determining the multidrug resistance (MDR) and plasmid profile of Staphylococcus aureus and Escherichia coli among patients attending Urology Clinic of Dalhatu Araf Specialist Hospital (DASH) Lafia, Nasarawa State, Nigeria. A total of two hundred and two (202) urine samples were collected in sterile containers and analyzed using standard microbiological techniques. Antibiotic susceptibility testing of the isolates was carried out using standard laboratory guidelines. Of the 202 samples analysed, 104 (51.4%) had significant bacteriuria. Staphylococcus aureus showed high resistance to Ampicillin, Amoxicillin, and Norfloxacin while E. coli was highly resistant to Rifampicin, Ampicilin, Ciprofloxacin and Ofloxacin. A total of 19 (18.27%) isolates were resistant to more than two different classes of antibiotics i.e. MDR. Out of the 19 MDR isolates, 11.29% were S. aureus while 19.35% were E. coli. These isolates were carrying plasmid for MDR ranging from 2500 base pair (bp) to 6000bp for S. aureus while 11,849bp for E. coli. Plasmids were therefore implicated to be responsible for drug resistance in most of the UTIs. Therefore, proper hygiene by individuals and public awareness policies by government agencies should be encouraged; and antibiotics for the treatment of UTIs should be based on these current antibiogram results.