Abstract Background The Freedom of Information Act (FOIA) provides access to unreleased government records that can be used to enhance the transparency and integrity of biomedical research. We characterized FOIA requests to Department of Health and Human Services (HHS) agencies, including request outcomes, processing times, backlogs, and costs. Methods Using HHS FOIA annual reports, we extracted data on the number of FOIA requests received and processed by HHS agencies between 2008 and 2017, as well as request outcomes. Processing times were reported in three time increments, < 1–20, 21–60, or 61+ days, and trends in backlog status were also described. Information about costs and fees collected were aggregated. Results Between 2008 and 2017, 69.6% of 530,094 HHS FOIA requests were received by the Centers for Medicare and Medicaid Services (CMS), 18.9% by the Food and Drug Administration (FDA), and 11.6% by all other HHS agencies. During this period, CMS processed 374,728 requests, FDA 114,938, and other HHS agencies 61,890. CMS and FDA reduced backlogged requests by 9396 (89.7%) and 4289 (65.3%), respectively, leaving backlogs of 1081 and 2279 requests at the end of 2017. CMS fully or partially granted 60.3% of requests whereas FDA fully or partially granted 72.4%. Of all requests to CMS, 82.0% were considered simple and 18.0% complex; 82.2% of simple requests and 54.9% of complex requests were processed in 20 days, and 5.6% and 29.9% were processed in 61+ days. In contrast, 60.2% of requests to FDA were considered simple and 39.8% complex; 28.8% of simple requests and 9.0% of complex requests were processed in 20 days, and 58.3% and 81.5% were processed in 61+ days. The costs to HHS associated with FOIA requests totaled $446.4 million ($809 per processed request), increasing from $28.1 million ($423 per request) in 2008 to $53.3 million ($1544 per request) in 2017. In total, HHS collected $8.5 million in fees (1.9% of total costs). Conclusions FOIA is frequently used to obtain information about HHS and its agencies. With growing costs, minimal fees collected, and lengthy processing times, HHS agencies’ FOIA programs might be made more efficient through greater proactive record disclosure.