Background: Improving family caregiver preparation for surrogate decision making is a critical priority. Objective: Determine a parsimonious set of intrapersonal factors associated with family caregivers' confidence in making future medical decisions for their relatives with cancer. Methods: Cross-sectional mail survey. Family caregivers of Medicare beneficiaries with pancreatic, lung, brain, ovarian, head and neck, hematologic, and stage IV cancers from communities of eight U.S. cancer centers. Participants completed validated measures of their social and mental health, self-care behaviors, coping styles, and surrogate decision-making confidence. Using linear modeling, the Bayesian information criterion was used to identify factors associated with decision-making confidence. A bootstrap approach was used to conduct penalized inference on the selected model coefficients. Model fit validation was assessed with a random forest ensemble. Results: Caregivers (n = 294) were on average 65.5 years old, mostly female (72.8%), and care recipients' spouse/partner (60.2%). The parsimonious set of factors associated with low caregiver decision-making confidence included less engagement in spiritual growth self-care, more use of avoidant coping, low emotional social support, and younger care recipient age (in-sample R 2 = 0.22). These factors were also identified by a random forest approach. After overfitting adjustment (shrunken R 2 = 0.09), the strongest associations with low surrogate decision-making confidence were low spiritual growth self-care (adjusted standardized B = 0.17, p = 0.005) and high use of avoidant coping (adjusted standardized B = -0.12, p = 0.049). Discussion: Identifying strategies to enhance spiritual growth and reduce avoidant coping may be promising targets for interventions to improve family caregivers' confidence in future surrogate decision making.