Moisture performance is a critical consideration for design and construction of energy-efficient buildings. This has become important as building energy codes have ramped up insulation requirements in recent years. Researchers from the Forest Service’s Forest Products Laboratory in Madison, Wisc., and Home Innovation Research Labs in Upper Marlboro, Md., collaborated to investigate moisture conditions in a variety of residential walls using two climate controlled test huts near Washington, DC. The main objective of this research was to identify moisture tolerant construction practices for highly insulated wood-frame exterior walls. Wall configurations varied in exterior cladding, water-resistive barrier, level of cavity insulation, presence of exterior continuous insulation, and interior vapor retarder. Temperature, relative humidity, and moisture content of wood framing and oriented strand board (OSB) sheathing were measured in both north- and south-facing wall orientations. Wintertime moisture accumulation was not significant in walls with an interior kraft vapor retarder, even though indoor humidity levels were elevated. Painted interior gypsum board alone was found not to be a reliable strategy for vapor control; it was too vapor permeable and resulted in significant moisture accumulation in OSB sheathing during winter. Computer simulations approximately captured the timing of seasonal changes in OSB moisture content, differences between north- and south-facing walls, and differences between walls with and without an interior kraft vapor retarder.