The U.S. Food and Drug Administration and National Cancer Institute are seeking to improve methods to evaluate cancer as a clinical outcome in postapproval studies of drug and device safety. Challenges to monitoring cancer outcomes include years-long latency periods for many cancers, difficulty in tracking patients over long periods of time, missing outcomes of interest if relying on reporting by patients or health care providers, burden of collecting high-quality, detailed documentation of incident cancers, and low statistical power for rarer cancers.Registration of incident cancers including patient identifiers occurs in every U.S. state. Yet, each state cancer registry is administered and must be accessed separately, which creates a nearly insurmountable burden of time, effort, and cost for postmarket surveillance in multiple or all states. A voluntary process is in development which would allow states to reduce these barriers and enhance the health and safety of their residents. Called the Virtual Pooled Registry-Cancer Linkage System, state cancer registries will continue to hold and control their registry data while having access to a more streamlined process for postmarket surveillance, providing better quality, complete, and more rapid discovery.A Web-based application and review process are in development with an additional effort devoted to highly automated linkage processes and federally compliant data file transmission security.The Food and Drug Administration and National Cancer Institute will have enhanced abilities to perform high-quality postmarket surveillance and other research at lower cost and with faster speed. This system also seeks to reduce cost and burden by participating state cancer registries. This process also supports the current modifications proposed by the U.S. Department of Health and Human Services and 15 other Federal Departments and Agencies to modernize, strengthen, and make more effective the Federal Policy for the Protection of Human Subjects known as the Common Rule.