Background The thumb trapeziometacarpal joint is one of the most common sites of arthritic degeneration prompting specialty care. Surgical treatment algorithms are based on radiographic arthritic progression. However, the pain and disability attributable to trapeziometacarpal arthritis do not correlate with arthritic stage, and depression has independently predicted poorer self-rated hand function both at baseline and after treatment in patients' atraumatic hand conditions. Questions/purposes (1) Does thumb trapeziometacarpal osteoarthritis impact both self-perceived general health and hand function? (2) Do depression and other comorbid conditions differentially impact patient-rated hand function based on the presence or absence of symptomatic trapeziometacarpal arthritis? (3) How do disease-specific, patient demographics and comorbid conditions impact selfreported hand function in patients with trapeziometacarpal osteoarthritis? Methods This cross-sectional study compared patients with symptomatic trapeziometacarpal osteoarthritis (n = 47) with matched control subjects without a symptomatic hand condition (n = 47). All participants self-reported medical (including depression) and musculoskeletal comorbidities and completed the SF-36 and the Michigan Hand Questionnaire (MHQ). Bivariate statistical analyses contrasted the patients with trapeziometacarpal osteoarthritis to control subjects. Linear regression modeling determined the impact of subject demographic data, comorbidity burden, and examination findings on total MHQ scores in patients with trapeziometacarpal arthritis. Results Patients with scored trapeziometacarpal osteoarthritis indicated poorer perceived general health on the SF-36 categories of limitations resulting from physical health (52 ± 29 versus 71 ± 31, mean difference 19 [95% confidence interval {CI}, 7-31], p = 0.003) and limitations resulting from emotional problems (50 ± 27 versus 67 ± 50, mean difference 17 [95% CI, 3-33], p = 0.022) compared with control subjects. Self-reported depression was associated with worse hand function (total MHQ score) in patients with trapeziometacarpal arthritis (69 ± 20 versus 49 ± 22: mean difference À20 [95% CI, À5 toÀ36], p = 0.012) but not in control patients (90 ± 13 versus 84 ± 20: mean difference À5 [95% CI, À8 to 19], p = 0.404). In multivariate modeling, depression (b À20, [95% CI, À5 to À34], p = 0.009) and upper extremity comorbidities (b À25, [95% CI, À10 to À40], p = 0.002) were both associated with reduced total MHQ scores in patients with trapeziometacarpal osteoarthritis, and those factors accounted for 34% of the variance in the MHQ score.