To examine associations between perceived ease of syringe access, syringe sources, injection behaviors, and law enforcement (LE) interactions among people who inject drugs (PWID) in rural Appalachian North Carolina (NC). Using respondent-driven sampling, a diverse sample of 309 self-reported PWID were recruited from rural Appalachian NC. Data were collected via audio computer-assisted self-interview technology from February 2019 through March 2020. Respondents reported demographics, sources of syringes, LE interactions, and injection behaviors. Univariate, bivariate, and linear regression analyses were performed. Respondents most often obtained syringes from pharmacies and syringe service programs (SSPs). Twenty-one percent disagreed that it was easy to obtain sterile syringes, with 28% reporting low or no access to an SSP. PWID who reported longer physical distances to an SSP had greater difficulty accessing syringes (P<.001). PWID who reported greater ease of access to syringes reported engaging in receptive syringe sharing less often (P<.01). PWID who were stopped and searched by LE more often reported injecting drugs somebody else prepared with nonsterile supplies more often (P<.01). Participants shared used injection supplies more than twice as often than they shared used syringes. These results underscore the importance of SSPs to mitigate the spread of human immunodeficiency virus and viral hepatitis in rural areas. Supporting mobile SSP services in rural areas could increase access to sterile syringes and injection supplies. SSPs should educate PWID about the importance of not sharing injection supplies. Pharmacies could increase syringe access in areas where SSPs do not operate.