As part its campus sustainability efforts, Pacific Northwest National Laboratory (PNNL) has invested in eight new and existing buildings to ensure they meet the U.S. Department of Energy’s requirements for high performance sustainable buildings (HPSB) at DOE sites. These investments are expected to benefit PNNL by reducing the total life-cycle cost of facilities, improving energy efficiency and water conservation, and making buildings safer and healthier for the occupants. This study examines the cost-effectiveness of the implementing measures that meet the criteria for HPSBs in 3 different types of buildings on the PNNL campus: offices, scientific laboratories, and data centers. In each of the three case studies examined the investments made to achieve HPSB status demonstrated a high return on the HPSB investments that have taken place in these varied environments. Simple paybacks for total investments in the three case study buildings ranged from just 2 to 5 years; savings-to-investment ratios all exceeded the desirable threshold of 1; and the net present values associated with these investments were all positive.