Meditation intervention studies are frequently undermined by lack of statistical power secondary to small sample size and/or threats to validity from high attrition. Consequently, the health benefits from meditation have been difficult to document. Unappreciated barriers to meditation are likely responsible for low enrollment and high attrition. The Determinants of Meditation Practice Inventory (DMPI) was developed to identify barriers to meditation, thereby allowing researchers to mitigate the barriers prior to intervention studies. A five step, mixed-methods approach, which included literature review, qualitative interviews with meditation teachers, content validation by an expert panel and community members, reliability testing, and construct validation with a sample of 150 cancer family caregivers, yielded the 17-item DMPI survey based on three content domains: perceptions and misconceptions, pragmatic concerns, and sociocultural beliefs. Data from the cancer family caregiver sample demonstrated Cronbach’s coefficient alpha of 0.87. Intraclass correlation for baseline and retest was 0.86 (C.I. 0.82–0.90). As an impediment profiler, the DMPI identifies barriers that can be addressed and overcome – leading to meditation interventions that are accessible to a larger segment of the population. Use of the DMPI will optimize meditation intervention research and help elucidate the health effects of meditation.