ABSTRACT: Understanding the distribution, antimicrobial resistance (AMR), and risk factors associated with multidrug-resistant (MDR) and methicillin-resistant staphylococci (MRS) isolated from cats admitted to veterinary clinics may decrease the risk of MDR and MRS transmission to humans and other cats. As such, the objectives of this study were to investigate the diversity in Staphylococcus spp. recovered from different anatomical locations in healthy and diseased cats and to determine the occurrence of MDR and MRS spp. as well as possible risk factors associated with colonization in these cats. Five swabs were collected from the anus, skin, ear canal, conjunctival sac, and nares of each cat (209 healthy and 191 diseased) admitted to a veterinary clinic in Eastern Province, Saudi Arabia, between January and December 2018. Prior to sample collection, cat owners completed a questionnaire collecting information on cat demographics, health status, management, and antimicrobial usage. In total, 179 Staphylococcus isolates were recovered from healthy (n = 71) and diseased (n = 108) cats, including 94 (52.5%) coagulase-positive staphylococci (CoPS), and 85 (47.5%) coagulase-negative staphylococci (CoNS). Five Staphylococcus spp. were identified, namely, Staphylococcus aureus, Staphylococcus pseudintermedius, Staphylococcus felis, Staphylococcus capitis, and Staphylococcus saprophyticus. Staphylococcus isolates were most commonly resistant to penicillin (56.4%) and ciprofloxacin (25.7%); however, no isolate was resistant to clindamycin. Thirty (16.8%) Staphylococcus spp. (24 S. aureus and 6 S. pseudintermedius) isolates were MDR, with resistance to up to six different antibiotic classes. Only 17 (9.5%) Staphylococcus spp. (15 methicillin-resistant S. aureus and 2 methicillin-resistant S. pseudintermedius) harbored the mecA gene. Risk factor analysis showed that cats with a history of antibiotic therapy, those raised mainly indoors with a child, and those who visit a veterinary clinic for treatment were at higher risk of MDR and MRS colonization. In conclusion, MDR and MRS were common in healthy and diseased cats in Saudi Arabia. Thus, an effective antimicrobial stewardship program and further studies using a One Health approach are required to investigate the role of cats as vectors for AMR transmission to humans.