BACKGROUND: Mobile health (mHealth) approaches offer potentially affordable ways to support the care of HIV-infected patients in overstretched health care systems. However, only few studies have analyzed the costs associated with mHealth solutions for HIV care. OBJECTIVE: The aim of this study was to estimate the total incremental costs and incremental cost per beneficiary of an interactive SMS text messaging support intervention within a clinical trial. METHODS: The Mobile WAChX trial (NCT02400671) evaluates an interactive semiautomated SMS text messaging intervention to improve adherence to antiretroviral therapy and retention in care among peripartum women infected with HIV in Kenya to reduce the mother-to-child transmission of HIV. Women were randomized to receive one-way versus two-way SMS text messages. Messages were sent weekly, and these messages included motivational and educational content and visit reminders; two-way messaging enabled prompt consultation with the nurse as needed. Microcosting methods were used to collect resource-use data related to implementing the Mobile WAChX SMS text messaging intervention. At 2 sites (Nairobi and Western Kenya), we conducted semistructured interviews with health personnel to identify startup and recurrent activities by obtaining information on the personnel, supplies, and equipment. Data on expenditures and prices from project expense reports, administrative records, and published government salary data were included to estimate the total incremental costs. Using a public provider perspective, we estimated incremental unit costs per beneficiary and per contact during 2017. RESULTS: The weighted average annual incremental costs for the two-way SMS text messaging group were US $3725 per facility, US $62 per beneficiary, and US $0.85 per contact to reach 115 beneficiaries. For the one-way SMS text messaging group, the weighted average annual incremental costs were US $2542 per facility, US $41 per beneficiary, and US $0.66 per contact to reach 117 beneficiaries. The largest cost shares were for the personnel: 48.2% (US $1794/US $3725) in two-way and 32.4% (US $825/US $2542) in one-way SMS text messaging groups. Costs associated with software development and communication accounted for 29.9% (US $1872/US $6267) of the costs in both intervention arms (US $1042 vs US $830, respectively). CONCLUSIONS: Cost information for budgeting and financial planning is relevant for implementing mHealth interventions in national health plans. Given the proportion of costs related to systems development, it is likely that costs per beneficiary will decline with the scale-up of the interventions.