BACKGROUND: Obesity, a multifactorial disease associated with many severe complications, affects more than 40% of adults in the United States. OBJECTIVE: To quantify the cost burden of 13 obesity-related complications (ORCs), overall and by body mass index (BMI) class. METHODS: Adult patients (aged ≥ 18 years) with ≥ 1 medical claim with an ICD-9/10 diagnosis code for the ORC of interest were identified using linked data from IQVIA's Ambulatory Electronic Medical Records and PharMetrics Plus. Thirteen ORCs were separately assessed (asthma, dyslipidemia, gastroesophageal reflux disease [GERD], heart failure with preserved ejection fraction [HFpEF], hypertension, musculoskeletal pain, obstructive sleep apnea [OSA], osteoarthritis [OA] of the knee, polycystic ovary syndrome [PCOS], prediabetes, psoriasis, type 2 diabetes mellitus [T2DM], and urinary incontinence); ORC cohorts were not mutually exclusive. For each ORC, the first claim identified for the ORC from January 2010-December 2016 was termed the index date. Patients had continuous enrollment in the 1-year pre-index (without a diagnosis code of the specific ORC under study) and the 1-year post-index, with ≥ 1 BMI value in the 6-months pre-index. Patients with underweight (BMI < 18.5 kg/m2) and those with cancer or pregnancy were excluded. Complication-specific costs were identified as claims with a diagnosis code for the ORC (primary position only for hospitalizations) or ORC-specific medications or procedures. Baseline demographic/clinical characteristics and complication-specific costs over the 1-year follow-up were assessed for each ORC cohort, overall and by BMI class (18.5-24.9; 25.0-29.9; 30.0-34.9; 35.0-39.9; ≥ 40 kg/m2). The association between total complication-specific costs and BMI class was assessed by generalized linear regression model for each ORC, adjusting for baseline characteristics. RESULTS: The total number of patients that comprised the ORC cohorts ranged from 1,275 (HFpEF) to 101,784 (musculoskeletal pain). Across ORC cohorts, 41.6% (musculoskeletal pain) to 73.5% (OSA) had obesity (BMI ≥ 30 kg/m2). For 4 ORC cohorts, more than one fifth of patients had class III obesity (BMI ≥ 40 kg/m2): T2DM, OSA, PCOS, and HFpEF. Baseline mean Charlson Comorbidity Index score increased with increasing BMI class for most ORC cohorts. The most costly ORCs overall based on mean total 1-year cost were: OA of the knee ($3,697 [range from normal weight (BMI: 18.5-24.9 kg/m2) to class III obesity: $2,453-$4,518]), HFpEF ($3,586 [range: $3,402-$4,685]), OSA ($2,768 [$2,442-$2,974]), and psoriasis ($2,711 [$2,131-$3,292]). The highest cost differences (≥20%) were observed among those with class III obesity versus those with normal weight for these aforementioned ORCs, as well as for GERD ($1,719 [$1,484-$1,893]) and asthma ($1,531 [$1,361-$1,780]). Following adjustment, most cost comparisons by BMI class were significantly higher versus those for normal weight for 6 ORCs. CONCLUSIONS: ORCs are important drivers of the economic burden of obesity, indicating an unmet need for the treatment of obesity. Appropriate weight management may reduce ORC-associated costs. DISCLOSURES: This study and its publication were supported by Novo Nordisk. Divino, Anupindi, and DeKoven are employed by IQVIA, which received funding from Novo Nordisk for this study. Ramasamy, Eriksen, Olsen, and Meincke are employed by and shareholders of Novo Nordisk. Material reported in this manuscript was presented in an abstract accepted by the International Society for Pharmacoeconomics and Outcomes Research (ISPOR) 2020, to be published in Value in Health. There was no presentation at ISPOR 2020.