© Stefanie Lynn Painter, Rezwan Ahmed, Robert F Kushner, James O Hill, Richard Lindquist, Scott Brunning, Amy Margulies. Background: Providing coaches as part of a weight management program is a common practice to increase participant engagement and weight loss success. Understanding coach and participant interactions and how these interactions impact weight loss success needs to be further explored for coaching best practices. Objective: The purpose of this study was to analyze the coach and participant interaction in a 6-month weight loss intervention administered by Retrofit, a personalized weight management and Web-based disease prevention solution. The study specifically examined the association between different methods of coach-participant interaction and weight loss and tried to understand the level of coaching impact on weight loss outcome. Methods: A retrospective analysis was performed using 1432 participants enrolled from 2011 to 2016 in the Retrofit weight loss program. Participants were males and females aged 18 years or older with a baseline body mass index of ≥25 kg/m2, who also provided at least one weight measurement beyond baseline. First, a detailed analysis of different coach-participant interaction was performed using both intent-to-treat and completer populations. Next, a multiple regression analysis was performed using all measures associated with coach-participant interactions involving expert coaching sessions, live weekly expert-led Web-based classes, and electronic messaging and feedback. Finally, 3 significant predictors (P<.001) were analyzed in depth to reveal the impact on weight loss outcome. Results: Participants in the Retrofit weight loss program lost a mean 5.14% (SE 0.14) of their baseline weight, with 44% (SE 0.01) of participants losing at least 5% of their baseline weight. Multiple regression model (R2=.158, P<.001) identified the following top 3 measures as significant predictors of weight loss at 6 months: expert coaching session attendance (P<.001), live weekly Web-based class attendance (P<.001), and food log feedback days per week (P<.001). Attending 80% of expert coaching sessions, attending 60% of live weekly Web-based classes, and receiving a minimum of 1 food log feedback day per week were associated with clinically significant weight loss. Conclusions: Participant’s one-on-one expert coaching session attendance, live weekly expert-led interactive Web-based class attendance, and the number of food log feedback days per week from expert coach were significant predictors of weight loss in a 6-month intervention.