© 2019 Journal of Medical Internet Research. All rights reserved. Background: As many as 50% of people experience medication nonadherence, yet studies for detecting nonadherence and delivering real-time interventions to improve adherence are lacking. Mobile health (mHealth) technologies show promise to track and support medication adherence. Objective: The study aimed to evaluate the feasibility and acceptability of using an mHealth system for medication adherence tracking and intervention delivery. The mHealth system comprises a smart button device to self-track medication taking, a companion smartphone app, a computer algorithm used to determine adherence and then deliver a standard or tailored SMS (short message service) text message on the basis of timing of medication taking. Standard SMS text messages indicated that the smartphone app registered the button press, whereas tailored SMS text messages encouraged habit formation and systems thinking on the basis of the timing the medications were taken. Methods: A convenience sample of 5 adults with chronic kidney disease (CKD), who were prescribed antihypertensive medication, participated in a 52-day longitudinal study. The study was conducted in 3 phases, with a standard SMS text message sent in phases 1 (study days 1-14) and 3 (study days 46-52) and tailored SMS text messages sent during phase 2 (study days 15-45) in response to participant medication self-tracking. Medication adherence was measured using: (1) the smart button and (2) electronic medication monitoring caps. Concordance between these 2 methods was evaluated using percentage of measurements made on the same day and occurring within ±5 min of one another. Acceptability was evaluated using qualitative feedback from participants. Results: A total of 5 patients with CKD, stages 1-4, were enrolled in the study, with the majority being men (60%), white (80%), and Hispanic/Latino (40%) of middle age (52.6 years, SD 22.49; range 20-70). The mHealth system was successfully initiated in the clinic setting for all enrolled participants. Of the expected 260 data points, 36.5% (n=95) were recorded with the smart button and 76.2% (n=198) with electronic monitoring. Concordant events (n=94), in which events were recorded with both the smart button and electronic monitoring, occurred 47% of the time and 58% of these events occurred within ±5 min of one another. Participant comments suggested SMS text messages were encouraging. Conclusions: It was feasible to recruit participants in the clinic setting for an mHealth study, and our system was successfully initiated for all enrolled participants. The smart button is an innovative way to self-report adherence data, including date and timing of medication taking, which were not previously available from measures that rely on recall of adherence. Although the selected smart button had poor concordance with electronic monitoring caps, participants were willing to use it to self-track medication adherence, and they found the mHealth system acceptable to use in most cases.