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Background Heart failure (HF) is associated with high mortality rates and high costs, and self-care is crucial in the management of the condition. Telehealth can promote patients’ self-care while providing frequent feedback to their health care providers about the patient’s compliance and symptoms. A number of technologies have been considered in the literature to facilitate telehealth in patients with HF. An important factor in the adoption of these technologies is their ease of use. Conversational agent technologies using a voice interface can be a good option because they use speech recognition to communicate with patients. Objective The aim of this paper is to study the engagement of patients with HF with voice interface technology. In particular, we investigate which patient characteristics are linked to increased technology use. Methods We used data from two separate HF patient groups that used different telehealth technologies over a 90-day period. Each group used a different type of voice interface; however, the scripts followed by the two technologies were identical. One technology was based on Amazon’s Alexa (Alexa+), and in the other technology, patients used a tablet to interact with a visually animated and voice-enabled avatar (Avatar). Patient engagement was measured as the number of days on which the patients used the technology during the study period. We used multiple linear regression to model engagement with the technology based on patients’ demographic and clinical characteristics and past technology use. Results In both populations, the patients were predominantly male and Black, had an average age of 55 years, and had HF for an average of 7 years. The only patient characteristic that was statistically different (P=.008) between the two populations was the number of medications they took to manage HF, with a mean of 8.7 (SD 4.0) for Alexa+ and 5.8 (SD 3.4) for Avatar patients. The regression model on the combined population shows that older patients used the technology more frequently (an additional 1.19 days of use for each additional year of age; P=.004). The number of medications to manage HF was negatively associated with use (−5.49; P=.005), and Black patients used the technology less frequently than other patients with similar characteristics (−15.96; P=.08). Conclusions Older patients’ higher engagement with telehealth is consistent with findings from previous studies, confirming the acceptability of technology in this subset of patients with HF. However, we also found that a higher number of HF medications, which may be correlated with a higher disease burden, is negatively associated with telehealth use. Finally, the lower engagement of Black patients highlights the need for further study to identify the reasons behind this lower engagement, including the possible role of social determinants of health, and potentially create technologies that are better tailored for this population.