Background Methamphetamine is associated with increased HIV risk and suboptimal adherence to pre-exposure prophylaxis (PrEP). Interventions to support PrEP adherence for people who use methamphetamine are needed. Methods We evaluated peer navigation to support adherence among people initiating PrEP who use methamphetamine. The HIV Prevention in Methamphetamine Users (HMU!) study enrolled participants from May 2018-January 2022 in Seattle, WA, and followed them for 6 months. Surveys collected sociodemographic, drug use, and sexual behavior data at enrollment, month 3, and month 6. Dried blood spots (DBS) were collected at months 1, 3, and 6 to measure PrEP adherence. Results We enrolled 21 participants of a target sample of 40, of whom 20 were prescribed PrEP. Nine participants (43%) received peer navigation and 12 (57%) received standard of care or text messaging. At baseline, most participants reported at least weekly methamphetamine use (17, 81%) and condomless receptive anal intercourse (CRAI) (16, 76%). One-third reported CRAI with a partner with HIV. Among those who provided a DBS, 78% and 50% had results commensurate with ≥4 pills/week at the month 3 and 6 visit, respectively. More than half of those prescribed PrEP completed a month 6 visit (11, 55%). Retention was not associated with peer support compared to standard of care or text messaging ( p = .20). Conclusions We enrolled half our target sample size despite extensive recruitment efforts. As expected, participants had challenges with PrEP adherence and persistence. While peer navigation interventions should be studied further, additional interventions are likely needed to support PrEP uptake, adherence, and persistence among people who use methamphetamine.