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BackgroundWhile mindfulness-based interventions (MBIs) employ two distinct practices, focused attention (FA) and open monitoring (OM), the integrated delivery of these practices in MBIs precludes understanding of their practice-specific effects or mechanisms of action. The purpose of this study is to isolate hypothesized active ingredients and practice-specific mechanistic target engagement by creating structurally equivalent interventions that differ only by the active ingredient (meditation practice) offered and to test whether the hypothesized components differentially engage the mechanistic targets that they are purported to engage. Methods Participants were intended to be representative of American meditators and had mild to severe affective disturbances. Measures of structural equivalence included participant-level (sample characteristics), treatment-level (program structure and duration, program materials, class size, attendance, homework compliance, etc.), and instructor-level variables (training, ratings and adherence/fidelity). Measures of differential validity included analysis of program materials and verification of differential mechanistic target engagement (cognitive and affective skills and beliefs about meditation acquired by participants after the 8-week training). Results The results indicate successful creation of structurally equivalent FA and OM programs that were matched on participant-level, treatment-level, and instructor-level variables. The interventions also differed as expected with respect to program materials as well as mechanistic targets engaged (skills and beliefs acquired). Conclusions These validated 8-week FA and OM training programs can be applied in future research to assess practice-specific effects of meditation.