A self-reported measure of four domains of work impairment based on the Work Limitations Questionnaire was completed by 16,651 employees of a large financial services corporation. Using a multivariate model to control for coexisting conditions, age, and gender, significant relationships were observed between medical conditions and patterns of impaired work performance. Depression was highly associated with work limitations in time management (odds ratio [OR] = 2.05), interpersonal/mental functioning (OR = 2.50), and overall output (OR = 2.24). Arthritis (OR = 1.56) and low back pain (OR = 1.32) were associated with physical function limitations. These same two conditions were associated with limitations in mental/interpersonal functioning but with low back pain having the higher odds ratio (OR = 1.54 vs. 1.22). These results suggest that worksite interventions (eg, disease management programs) should be tailored to the unique effects observed with specific medical conditions. More targeted programs could have important benefits for productivity in the workplace.