The use of drones in the health care sector is increasingly being discussed against the background of the aging population and the growing shortage of skilled workers. In particular, the use of drones to provide medication in rural areas could bring advantages for the care of people with and without a need for care. However, there are hardly any data available that focus on the interaction between humans and drones. This study aims to disclose and analyze factors associated with user acceptance of drone-based medication delivery to derive practice-relevant guidance points for participatory technology development (for apps and drones). A controlled mixed methods study was conducted that supports the technical development process of an app design for drone-assisted drug delivery based on a participatory research design. For the quantitative analysis, established and standardized survey instruments to capture technology acceptance, such as the System Usability Scale; Technology Usage Inventory (TUI); and the Motivation, Engagement, and Thriving in User Experience model, were used. To avoid possible biasing effects from a continuous user development (eg, response shifts and learning effects), an ad hoc group was formed at each of the 3 iterative development steps and was subsequently compared with the consisting core group, which went through all 3 iterations. The study found a positive correlation between the usability of a pharmacy drone app and participants' willingness to use it (r=0.833). Participants' perception of usefulness positively influenced their willingness to use the app (r=0.487; TUI). Skepticism had a negative impact on perceived usability and willingness to use it (r=-0.542; System Usability Scale and r=-0.446; TUI). The study found that usefulness, skepticism, and curiosity explained most of the intention to use the app (F3,17=21.12; P<.001; R2=0.788; adjusted R2=0.751). The core group showed higher ratings on the intention to use the pharmacy drone app than the ad hoc groups. Results of the 2-tailed t tests showed a higher rating on usability for the third iteration of the core group compared with the first iteration. With the help of the participatory design, important aspects of acceptance could be revealed by the people involved in relation to drone-assisted drug delivery. For example, the length of time spent using the technology is an important factor for the intention to use the app. Technology-specific factors such as user-friendliness or curiosity are directly related to the use acceptance of the drone app. Results of this study showed that the more participants perceived their own competence in handling the app, the more they were willing to use the technology and the more they rated the app as usable.