OBJECTIVES: To estimate annual medical expenditure (ME) and lost productivity cost (PC) attributable to chronic diseases in working U.S. adults. METHODS: A cross-sectional design, using the 2003-2006 Medical Expenditure Panel Survey data was employed. We identified working adults who were 18-64 years old and classified them as having chronic diseases (arthritis, asthma, hypertension, hypercholesterolemia, or diabetes) or not.  We excluded patients with malignancy, kidney dialysis, immunodeficiency, pregnancy, or BMI<18.5. MEs were estimated using a generalized linear model with log link function and gamma distribution. PC was calculated based on missed working days due to illness and average hourly wage, using a two-part model.  Costs attributable to chronic diseases were estimated by differences between actual and expected cost in patients with chronic diseases, using a distribution of covariates obtained from all patients.  Treatment costs were converted to 2008 U.S. dollars using price indices.  RESULTS: Among the identified 54,843 working adults, a third (34%) had at least one of five chronic diseases. Patients with two or ≥three chronic diseases accounted for 8.5% and 3.7%, respectively.  The average ME in patients with chronic diseases was significantly higher than individuals without those diseases ($2997; 95%CI=$2865-$3129 vs. $1021; 95%CI=$911-$1130). The average PC in these patients showed a similar trend ($481; 95%CI=$455-$507 vs. $236; 95%CI=$219-$253).   Excess ME attributable to chronic diseases were estimated at $1605 (95%CI:$1501-$1710) and excess PC at $173 (95%CI $172-$ 174).  ME and PC increased with an increase in concurrent chronic diseases, respectively.  Among the chronic diseases, arthritis and diabetes were the largest contributors to additional economic burden. CONCLUSIONS: The presence of chronic diseases in working patients resulted in significantly higher ME and PC. The results highlight the additional economic burden attributable to chronic diseases in the working population and the need to allocate resources toward better management strategies for these diseases.