Background <p>Rural people who use drugs face a litany of structural and psychosocial barriers to SSP utilization (e.g., unreliable transportation, stigma). Mobile SSPs may mitigate some barriers, but little is known about acceptability among rural people who use drugs and their preferences for mobile SSP design. This study examines (1) factors associated with willingness to use a mobile SSP among rural people who use drugs, and (2) their desired attributes and services.</p> Methods <p>Data were collected from 259 participants who inject drugs that were recruited through outreach and respondent-driven sampling (RDS) in Appalachian Kentucky. In addition to descriptive analyses, independent variables’ associations with the outcome (i.e., being willing to use a mobile SSP) were estimated using generalized estimating equations. All models controlled for lifetime use of a fixed-site SSP.</p> Results <p>Overall, 59.9% (n = 155) endorsed mobile SSPs as a program they would be willing to use. People with lower income, had less reliable access to transportation, were using methamphetamine, were engaging in syringe sharing and reuse, and who had experienced more overdoses in their lifetime were more willing to use a mobile SSP than were their counterparts. Those who experienced more shame around their drug use were less likely to use a mobile SSP than those who experienced no shame. Participants were receptive to a variety of locations, unit sizes, and staffing models, but the most desired staffing and locations were clinical in nature and most preferred hours of operation were afternoon hours.</p> Discussion <p>Findings suggest moderate willingness to engage in mobile SSP services among this population, particularly for people who use drugs who have challenges with transportation and who are engaging in behaviors that increase risk for HIV and HCV. Mobile SSPs may increase accessibility, acceptability, and ultimately, the utilization of critical harm reduction services in Appalachia.</p>