OBJECTIVES:  Renal failure (RF) imposes a significant burden on patients, providers, payers, and society. Economic evaluation from a national representative data isn’t well-documented. Therefore, the aim of our study was to comprehensively evaluate the direct and indirect cost of RF in the USA. METHODS:  A cross-sectional study was performed using MEPS 2008-2013. Direct healthcare (HC) cost and indirect cost (employment, wages, missed days, and cost to loss of productivity LOP) were compared between adults with and without RF. Propensity score matching (PS) to control for baseline differences and linear regression with logarithmic transformation to identify predictors of total healthcare expenditure were incorporated. All expenses were adjusted to 2016 USD. RESULTS:  There was a total of 466 (0.31%) adults with RF compare to 148,045 without RF. RF patients had significantly (p<.0001) higher prevalence of hypertension, diabetes and other important comorbid conditions. With PS, 394 RF were matched to 788 no-RF (1:2 ratio) and the average annual cost per person were $40,804 vs. $15,851 (additional cost = $24,953, p<.0001). Events coded RF-specific had average annual cost of $16,708 per person. Compared to no-RF, patients experienced significant extra expenses (p<.02) for medications, ambulatory care and medical supplies due to RF disease. RF was significantly associated with lower employment (p<.0001), wages (p<.0001) and more missed days (p<.0034) but insignificant associations were observed post PS matching. The per person annual indirect cost of LOP for RF Patients was $42,893 before propensity score matching and $12,466 after (2016 UD dollars). For RF patients, age, gender, ethnicity, region, poverty level, education, insurance type, smoking, key comorbidities and perceived health status were identified as significant independent predictors (p<.0001) for direct total healthcare utilization cost. CONCLUSIONS:  Compared to the general population, RF is associated with significant economic burden. Further investigation of the causes of higher utilization and expenses in this group is recommended.