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Aims Cost-effectiveness (CE) of lifestyle change programs (LCP) for type 2 diabetes (T2D) prevention is influenced by a participant's risk. We identified the risk threshold of developing T2D in the intervention population that was cost-effective for three formats of the LCP: delivered in-person individually or in groups, or delivered virtually. We compared the cost-effectiveness across program formats when there were more than one cost-effective formats. Methods Using the CDC-RTI T2D CE Simulation model, we estimated CEs associated with 3 program formats in 8 population groups with an annual T2D incidence of 1% to 8%. We generated a nationally representative simulation population for each risk level using the 2011–2016 National Health and Nutrition Examination Survey data. We used an incremental cost-effectiveness ratio (ICER), cost per quality-adjusted life year (QALY) gained in 25-years, to measure the CEs of the programs. We took a health care system perspective. Results To achieve an ICER of $50,000/QALY or lower, the annual T2D incidence of the program participant needed to be ≥5% for the in-person individual program, ≥4% for the digital individual program, and ≥3% for the in-person group program. For those with T2D risk of ≥4%, the in-person group program always dominated the digital individual program. The in-person individual program was cost-effective compared with the in-person group program only among persons with T2D risk of ≥8%. Conclusions Our findings could assist decision-makers in selecting the most appropriate target population for different formats of lifestyle intervention programs to prevent T2D.