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BACKGROUND: Online interventions can be a cost-effective and efficient way to deliver programs to large numbers of people regardless of geographic location. However, attrition in web-based interventions is often an issue. Developing ways to keep participants engaged is important for ensuring validity and limiting potential biases. We developed a web-based dietary intervention as part of The My Food & Mood study which aimed to optimize ways to engage participants with low mood or depressive symptoms to promote dietary behavior change. Different versions of the My Food & Mood program were tested during optimization. Iterations were developed based on user feedback and usage analysis. OBJECTIVE: The purpose of this study was to compare engagement and nonusage attrition across 4 program iterations-which differed by platform format, delivery mode, and activity type-to create an optimized version. METHODS: Each program version contained modular videos with key activities with respect to implementing behavior change techniques of equivalent levels of required participation and length: version 1.0, desktop program and smartphone app; version 2.1, desktop or smartphone program; version 2.2, desktop program; and version 3.0, smartphone app. Adults with PHQ-8 scores of 5 or greater were recruited online and assigned to 1 of the 4 versions. Participants were asked to use the program for 8 weeks and complete measures at weeks 4 and 8. Engagement data were collected from the web-based platform system logs and customized reports. Cox regression survival analysis examined nonusage attrition and Kruskal-Wallis tests compared engagement across each cohort. RESULTS: A total of 614 adults participated. Kruskal-Wallis tests showed significant differences across the 4 cohorts in all engagement measures. The smartphone app (version 3.0) had the greatest engagement as measured by weeks engaged, total usage time, total time key activities, number of active sessions, percentage of activities