Drug use disorders (DUDs) can substantially increase the costs of health care, especially when left untreated. Yet, not much is known about the specific types of medical services that give rise to these cost differences. This study aimed to estimate the medical costs of beneficiaries with DUDs enrolled in the Medicaid Managed Care (MMC) program in Puerto Rico using claims data. These were compared to those of a matched group of patients without DUDs. On average, each beneficiary with a DUD incurred in $4539 annually on medical services compared to $2601 in the matched comparison group, a cost differential of $1938. Close to half of these additional medical costs (43.4%) were generated in the physical health services sector. Counts of service claims were also higher for beneficiaries with DUDs than for beneficiaries without DUDs in all service types, except in outpatient and laboratory services for physical health. A host of access strategies and treatment modalities should be tested to assess the extent to which providing adequate access and adequate treatment for a DUD can contribute to cost savings.