BACKGROUND: Diabetes is a highly prevalent and costly disease. Studies indicate that combined diet and physical activity promotion programs can prevent type 2 diabetes among persons at increased risk. PURPOSE: To systematically evaluate the evidence on cost, cost-effectiveness, and cost-benefit estimates of diet and physical activity promotion programs. DATA SOURCES: Cochrane Library, EMBASE, MEDLINE, PsycINFO, Sociological Abstracts, Web of Science, EconLit, and CINAHL through 7 April 2015. STUDY SELECTION: English-language studies from high-income countries that provided data on cost, cost-effectiveness, or cost-benefit ratios of diet and physical activity promotion programs with at least 2 sessions over at least 3 months delivered to persons at increased risk for type 2 diabetes. DATA EXTRACTION: Dual abstraction and assessment of relevant study details. DATA SYNTHESIS: Twenty-eight studies were included. Costs were expressed in 2013 U.S. dollars. The median program cost per participant was $653. Costs were lower for group-based programs (median, $417) and programs implemented in community or primary care settings (median, $424) than for the U.S. DPP (Diabetes Prevention Program) trial and the DPP Outcomes Study ($5881). Twenty-two studies assessed the incremental cost-effectiveness ratios (ICERs) of the programs. From a health system perspective, 16 studies reported a median ICER of $13 761 per quality-adjusted life-year (QALY) saved. Group-based programs were more cost-effective (median, $1819 per QALY) than those that used individual sessions (median, $15 846 per QALY). No cost-benefit studies were identified. LIMITATION: Information on recruitment costs and cost-effectiveness of translational programs implemented in community and primary care settings was limited. CONCLUSION: Diet and physical activity promotion programs to prevent type 2 diabetes are cost-effective among persons at increased risk. Costs are lower when programs are delivered to groups in community or primary care settings.