Background: Prior studies have suggested that patient-rated hand function is impacted by depression and pain catastrophization. We studied the impact that these comorbidities have on treatment outcomes. Methods: Two hundred and fifty-six patients presenting to an orthopaedic hand clinic were followed in this prospective cohort investigation. Patients who were prescribed treatment for atraumatic hand/wrist conditions were eligible for inclusion. At enrollment, all patients completed the Center for Epidemiologic Studies Depression (CES-D) scale, the Pain Catastrophizing Scale (PCS), and the Michigan Hand Outcomes Questionnaire (MHQ; scale of 0 to 100, with 100 indicating the best hand performance). One month and three months after treatment, patients again completed the MHQ. Participants' psychological comorbidity status was categorized as either affected (a CES-D score of ≥16, indicating depression, or a PCS score of ≥30, indicating catastrophization) or unaffected (a CES-D score of <16 and a PCS score of <30). Diagnoses and treatments for both the affected and unaffected groups were examined. The effect of time and patient status, and their interaction, on MHQ scores was evaluated by mixed modeling. Results: Fifty patients were categorized as affected and 206 as unaffected. Diagnoses and treatments differed minimally between the two groups. At the time of enrollment, themeanMHQ score of the unaffected group (64.9; 95% confidence interval [CI], 62.5 to 67.3) was significantly higher than that of the affected group (48.1; 95% CI, 43.3 to 53.0). Both groups demonstrated similar significant absolute improvement over baseline at three months after treatment (an increase of 12.5 points [95% CI, 7.5 to 17.4] in the affected group and 12.8 points [95% CI, 10.4 to 15.3] in the unaffected group). Thus, at the time of final follow-up, the rating of hand function by the affected patients (60.6 [95% CI, 55.0 to 66.2]) was still significantly poorer than the rating by the unaffected patients (77.7 [95% CI, 75.0 to 80.5]). Conclusions: Although patients affected by depression and/or pain catastrophization reported worse self-rated hand function at baseline and at the time of follow-up, these patients showed similar absolute improvement in self-rated hand function following treatment compared with patients with unaffected status. Level of Evidence: Prognostic Level I. See Instructions for Authors for a complete description of levels of evidence.