OBJECTIVES: Limited data exist on the economic impact of SLE flares. This study estimated HRU and costs of SLE flares in a U.S. Medicaid population. METHODS: SLE Patients ≥18 years old were extracted from a large Medicaid database 2002-2009. Index date was the date of the first SLE diagnosis. All patients were continuously enrolled for ≥6 months before and ≥12 months after index date and followed until the earliest of inpatient death, end of enrollment, or end of study. Mild, moderate, and severe flares were identified in the follow-up period. Costs attributable to flares were measured during 30 days following a flare. If a flare of higher severity occurred within 30 days, the length was limited to the period up to the start of the new flare. RESULTS: 14,262 patients met the study criteria and 97% experienced at least one flare during an average follow-up of 39 months (3,540 had severe, 9,597 had moderate, and 669 had mild flares as their most severe flares). Mean costs per flare were $11,716, $562 and $129 for severe, moderate, and mild flares, respectively. Patients with ≥1 severe flares during follow-up had 1.7 inpatient (IP) admissions, 3.5 emergency room (ER) visits, and 16.0 outpatient (OP) visits with a total medical cost of $49,754per year. Patients with ≥1 moderate flares but no severe flares had 0.9 IP admissions, 2.4 ER visits, and 12.8 OP visits with a cost of $21,941. Patients with only mild flares had the least HRU of 1.0 IP admission, 1.5 ER visits, and 7.5 OP visits with a cost of $17,574. Patients with severe and moderate but no mild flares and patients with severe flares only incurred the highest annual cost ($66,412 and $74,491, respectively). CONCLUSIONS: Flares occurred in almost all SLE patients and were associated with a significant economic burden.