Early identification and treatment of Staphylococcus aureus (S. aureus) nasal colonization can reduce the risk of prosthetic joint infection. The purpose of this study was to evaluate patient-specific predictors for S. aureus nasal colonization in total joint arthroplasty patients to aid in preoperative screening protocols. A total of 2,147 arthroplasty patients who were preoperatively screened for S. aureus nasal colonization were retrospectively reviewed. Factors analyzed consisted of procedure type, primary diagnosis, gender, ethnicity, body mass index, the presence of chronic obstructive pulmonary disease, obstructive sleep apnea, hypertension, diabetes mellitus, use of immunosuppression medication, smoking history, and chronic kidney disease. Univariate and multivariate analyses were performed with significance p < 0.05 and 95% confidence intervals. Overall, 3.7% (79) of our cohort tested positive for methicillin-resistant Staphylococcus aureus (MRSA), and 23.2% (493) tested positive for methicillin-sensitive Staphylococcus aureus (MSSA). Independent predictors for MRSA colonization were of Hispanic ethnicity (p = 0.001, odds ratio [OR] 13.98, confidence interval [CI] 2.97–65.76), immunosuppression medication use (p = 0.006, OR 2.82, CI 1.35–5.87), and revision total hip arthroplasty (THA) procedure (p < 0.001, OR 7.51, CI 2.58–21.89). Independent predictors for MSSA colonization were body mass index (BMI) >35 (p = 0.002, OR 1.57, CI 1.19–2.1). Variables were found to be protective against MSSA colonization including female gender (p = 0.012, OR 0.76, CI 0.61–0.94), age 60 to 69 (p = 0.025, OR 0.75, CI 0.58–0.96), and age 70 to 79 (p = 0.002, OR 0.63, CI 0.47–0.84). Age, Hispanic ethnicity, gender, revision THA, use of immunosuppression medication, and elevated BMI were independent risk factors for S. aureus nasal colonization.