The paucity of data regarding the extent of Hepatitis delta virus (HDV) associated healthcare burden in the United States is an important obstacle to assessing the cost-effectiveness of potential intervention strategies. In this study, we characterized the healthcare utilization and cost burdens of HDV in the US using real-world claims data. We conducted a case-control study using the Truven Health MarketScan® Commercial Claims databases from 2011-2014. A total of 2,727 HDV cases were matched 1:1 by sociodemographic characteristics and comorbidities to chronic Hepatitis b virus (HBV) controls using propensity scores. The HDV group had significantly higher prevalence of substance abuse, sexually transmitted diseases, decompensated cirrhosis, cirrhosis and hepatitis c virus compared to chronic HBV patients. First HDV diagnosis was associated with significant increases in the total number of healthcare claims (25.61 vs. 28.99; P < 0.0001) and total annual healthcare costs ($19,476 vs. $23,605; P < 0.0001) compared to pre-HDV baseline. The case-control analysis similarly indicated higher total claims (28.99 vs. 25.19; P < 0.0001) and healthcare costs ($23,605 vs. $18,228; P < 0.0001) in HDV compared to the HBV alone. Compared to HBV controls, HDV Cases had adjusted Incident Rate Ratio (aIRR) 1.16 (95% CI; 1.10, 1.22) times the total number of annual claims and aIRR 1.32 (95% CI; 1.17, 1.48) times the total annual healthcare cost. HDV is associated with higher healthcare utilization and cost burden than HBV alone, underscoring the need for improved screening and treatment.