BACKGROUND: Recent studies have found that depression is associated with increased pain and impairment following lower-extremity arthroplasty; however, this association has not been investigated for total shoulder arthroplasty. The objective of this study was to investigate the association between depression and patient-reported outcomes following total shoulder arthroplasty. METHODS: A prospectively collected institutional registry was queried for consecutive patients who underwent total shoulder arthroplasty for osteoarthritis from 2007 to 2013 with baseline and minimum 2-year postoperative American Shoulder and Elbow Surgeons (ASES) scores. Revision procedures and total shoulder arthroplasty for diagnoses other than osteoarthritis were excluded. Patients with a preoperative diagnosis of depression (n = 88) formed the study cohort; control patients without a diagnosis of depression were matched to the study patients by age and sex in a 2:1 ratio (n = 176). Baseline characteristics and patient-reported outcome measures were compared between groups, as were minimum 2-year patient-reported outcomes and change in patient-reported outcomes. A multivariable regression was performed to investigate the independent effect of depression on improvement in ASES scores. RESULTS: Except for the Short Form-12 Mental Component Summary (SF-12 MCS) scores, there were no significant differences (p > 0.05) in baseline characteristics between study patients and controls. There was a significant improvement in the ASES score for patients with depression (p < 0.0001) and controls (p < 0.0001). Patients with depression had significantly lower final ASES scores (p = 0.001) and less improvement in ASES scores (p = 0.001) and SF-12 Physical Component Summary scores (p = 0.006) as well as lower satisfaction levels at 2 years; however, the latter difference did not reach clinical importance. Depression (p = 0.018) was an independent predictor of less improvement in ASES scores. CONCLUSIONS: Patients with a diagnosis of depression should be counseled that they will experience a significant clinical improvement from baseline after total shoulder arthroplasty. A preoperative diagnosis of depression is an independent predictor of significantly less improvement in ASES scores following total shoulder arthroplasty; however, this difference does not reach clinical importance and should not discourage patients with a clinical diagnosis of depression from undergoing total shoulder arthroplasty.