Home specimen self-collection kits with central laboratory testing may improve persistence with PrEP and enhance telehealth programs. We offered Iowa TelePrEP clients the choice of using a home kit or visiting a laboratory site for routine monitoring. Mixed-methods evaluation determined the proportion of clients who chose a kit, factors influencing choice, associations between kit use and completion of indicated laboratory monitoring, and user experience. About 46% (35/77) chose to use a kit. Compared to laboratory site use, kit use was associated with higher completion of extra-genital swabs (OR 6.33, 95% CI 1.20–33.51, for anorectal swabs), but lower completion of blood tests (OR 0.21, 95% CI 0.06–0.73 for creatinine). Factors influencing choice included self-efficacy to use kits, time/convenience, and privacy/confidentiality. Clients reported kit use was straight-forward but described challenges with finger prick blood collection. Telehealth PrEP programs should offer clients home kits and support clients with blood collection and kit completion.