The Early Phase Pain Investigation Clinical Network (EPPIC-Net) is part of the trans-NIH Helping to End Addiction Long-term (HEAL) initiative. The role of EPPIC-Net is to help speed scientific solutions to stem the national opioid public health crisis via early-phase clinical trials of non-addictive pain therapeutics (assets). EPPIC-Net's infrastructure includes a clinical coordinating center (responsible for protocol development, trial management, and site/investigator training), a data coordinating center (responsible for data management, statistical support, and quality assurance), and 12 specialized clinical centers (SCCs; that conduct procedures and supply pain expertise and wide outreach into diverse pain communities) across the United States. EPPIC-Net has capacity to run several multisite trials simultaneously. Assets for studies are selected through a 3-stage application and review process. Opportunities for training and mentorship are offered through HEAL-funded K awards and supplements. EPPIC-Net is committed to a patient-centered approach to pain management. Focus groups solicit and synthesize patient input to help inform EPPIC-Net's studies, while working groups identify and reduce barriers to enrollment. A patient-oriented website will provide informational and educational materials designed to raise awareness of the network, recruit diverse patient populations, and engage community stakeholders. EPPIC-Net has approved funding for three trials thus far and continues to accept applications on a rolling basis. Two EPPIC-Net investigators have received K24 mentorship awards and two SCCs have received supplement awards for innovative approaches to enhance recruitment/retention of diverse populations. Three diversity training and three career enhancement supplements were awarded to meritorious trainees.