BACKGROUND: The general public is largely aware of meditation, and there is compelling evidence the practice has health benefits. But many people who are aware of meditation have not tried it, and those who do often struggle to establish a regular practice. The barriers to meditation are generally understood and include a lack of knowledge, a lack of time, and unclear benefits. These barriers present an impediment to self-efficacy in establishing a meditation practice. Despite these challenges, current strategies for promoting meditation may fail to address these barriers, leaving a gap in our knowledge about health communication efforts aimed at fostering meditation practices. OBJECTIVE: The objective of this research is to leverage a large-scale, real-world digital platform to understand whether breaking down the theory-based barriers to meditation can serve as an effective strategy for encouraging meditation. METHODS: This research is a digital messaging-based experiment that includes approximately 1.33 million people, aged 18 years and older, in the United States. The experiment was conducted on the Spotify mobile app and includes 1 control condition and 4 test conditions. Each of the test conditions was a message that attempted to address a specific barrier to meditation. The control message only included the call-to-action without any theory-based messaging accompaniment. When users clicked the message, they were redirected to meditation content. The click-through rate and the activation rate of each message were the dependent variables in the experiment. RESULTS: The most effective message, which was designed to break down the pragmatic barriers to meditation, had a click-through rate odds ratio (OR) of 1.57 (95% CI 1.52-1.62) and an activation rate OR of 1.55 (95% CI 1.45-1.65), relative to the control. The least effective, which was designed to break down knowledge barriers, had a click-through rate OR of 0.91 (95% CI 0.88-0.94) and an activation rate OR of 0.66 (95% CI 0.61-0.71), compared to the control. After 7 days, the differences in people's engagement with the meditation content itself between experimental conditions had substantively diminished. CONCLUSIONS: Theory-driven messaging can potentially encourage people to explore meditation content, but not universally so, given 2 of the experimental conditions performed better than and 2 performed worse than the control. The most successful message broke down the barrier that meditation requires being alone and in a quiet place. Addressing this barrier may have boosted self-efficacy by aligning the practice with everyday settings that fit into people's busy lifestyles. Future researchers might consider how to encourage people to engage in meditation during their daily activities. In addition, breaking down the barriers to meditation through messaging can drive interest and experimentation with meditation content, but may not be enough to compel meaningful behavior change.