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Introduction: To determine the effects of a novel lifestyle intervention combining lifestyle behavioral education with the complementary-integrative health modality of guided imagery (GI) on dietary and physical activity behaviors in adolescents. The primary aim of this study was to determine the incremental effects of the lifestyle education, stress reduction GI (SRGI), and lifestyle behavior GI (LBGI) components of the intervention on the primary outcome of physical activity lifestyle behaviors (sedentary behavior, light, moderate, and vigorous physical activity), as well as dietary intake behaviors, at the completion of the 12-week intervention. The authors hypothesized that the intervention would improve obesity-related lifestyle behaviors. Materials and Methods: Two hundred and thirty-two adolescent participants (aged 14-17 years, sophomore or junior year of high school) were cluster randomized by school into one of four intervention arms: nonintervention Control (C), Lifestyle education (LS), SRGI, and LBGI. After-school intervention sessions were held two (LS) or three (SRGI, LBGI) times weekly for 12 weeks. Physical activity (accelerometry) and dietary intake (multiple diet recalls) outcomes were assessed pre- and postintervention. Primary analysis: intention-to-treat (ITT) mixed-effects modeling with diagonal covariance matrices; secondary analysis: ad hoc subgroup sensitivity analysis using only those participants adherent to protocol. Results: ITT analysis showed that the Healthy Eating Index (HEI) increased in the LS group compared with C ( p  = 0.02), but there was no additional effect of GI. Among adherent participants, sedentary behavior was decreased stepwise relative to C in SRGI ( d  = -0.73, p  = 0.004) > LBGI ( d  = -0.59, p  = 0.04) > LS ( d  = -0.41, p  = 0.07), and moderate + vigorous physical activity was increased in SRGI ( d  = 0.58, p  = 0.001). Among adherent participants, the HEI was increased in LS and SRGI, and glycemic index reduced in LBGI. Conclusions: While ITT analysis was negative, among adherent participants, the Imagine HEALTH lifestyle intervention improved eating habits, reduced sedentary activity, and increased physical activity, suggesting that GI may amplify the role of lifestyle education alone for some key outcomes. Clinical Trials.gov ID: NCT02088294.