Background: This study investigated the utility of depression and anxiety symptom screening in patients scheduled for total knee arthroplasty to examine differences in active symptoms according to patients’ mental health diagnoses and associated prescription medications. Material and methods: This cross-sectional study analyzed 594 patients scheduled for total knee arthroplasty at a tertiary practice between June 2018 and December 2018. Patients completed Patient-Reported Outcomes Measurements Information System (PROMIS) Depression and Anxiety Computerized Adaptive Tests in clinic quantifying active symptoms. Mental health diagnoses and associated medications were extracted from health records. Statistical analysis assessed between-group differences in mean PROMIS scores and the prevalence of heightened depressive and anxiety symptoms. Results: Multivariable linear regression modeling demonstrated that being diagnosed with depression without medication (β 7.1; P < .001) and with medication (β 8.6; P < .001) were each associated with higher PROMIS Depression scores. Similar modeling demonstrated that patients diagnosed with anxiety and prescribed an anxiolytic (β 8.4; P < .001) were associated with higher PROMIS Anxiety scores than undiagnosed patients. Eighty-six (15%) patients experienced heightened anxiety and/or depressive symptoms. Heightened depressive symptoms were more prevalent among those diagnosed with depression (19% without medication, 24% with antidepressant vs 5% undiagnosed: P < .001). Heightened anxiety symptoms were most prevalent among those diagnosed with anxiety and on anxiolytic medication (25% vs 7% diagnosed with anxiety without medication, 8% undiagnosed: P < .001). Conclusion: One in seven arthroplasty patients screened reported heightened depressive and/or anxiety symptoms. Despite the majority of arthroplasty patients on antidepressants and anxiolytics having symptoms controlled, these patients remain at increased risk of heightened active symptoms.