Objective: Depression is more common among persons with multiple sclerosis (MS) than the general population. Depression in MS is associated with reduced quality of life, transition to unemployment, and cognitive impairment. Two proposed screening measures for depression in MS populations are the Hospital Anxiety and Depression Scale (HADS) and the Beck Depression Inventory-Fast Screen (BDI-FS). Our objective was to compared the associations of the BDI-FS and the HADS-D scores with history of depressive symptoms, fatigue, and functional outcomes to determine the differential clinical utility of these screening measures among persons with MS. Method: We reviewed charts of 133 persons with MS for demographic information; scores on the HADS, BDI-FS, a fatigue measure, and a processing speed measure; and employment status. Results: Structural equation modeling results indicated the HADS-D predicted employment status, disability status, and processing speed more effectively than did the BDI-FS, whereas both measures predicted fatigue. Conclusions: This study suggests the HADS-D is more effective than the BDI-FS in predicting functional outcomes known to be associated with depression among persons with MS.