This study evaluates energy performance and economic analysis of variable refrigerant flow (VRF) systems in U.S. climate locations using widely-accepted whole building energy modeling software, EnergyPlus. VRF systems are known for their high energy performance and thus can improve energy efficiency in buildings. To evaluate the energy performance of a VRF system, energy simulation modeling and calibration of a VRF heat pump (HP) type system is performed using the EnergyPlus program based on measured data collected from an experimental facility at Oak Ridge National Laboratory (ORNL). In the calibration procedures, the energy simulation model is calibrated, according to the ASHRAE Guideline 14-2014, under cooling and heating seasons. After a proper calibration of the simulation model, the VRF HP system is placed in U.S. climate locations to evaluate the performance variations in different weather conditions. An office prototype building model, developed by the U.S. Department of Energy (DOE), is used with the VRF HP system in this study. This study also considers net-zero energy building (NZEB) design of VRF systems with a distributed photovoltaic (PV) system. The NZEB concept has been considered as one of the remedies to reduce electric energy usages and achieve high energy efficiency in buildings. Both the VRF HP and VRF heat recovery (HR) system types are considered in the NZEB design, and a solar PV system is utilized to enable NZEB balances in U.S. climate locations by assuming that net-metering available within the electrical grid-level. In addition, this study conducts life cycle cost analysis (LCCA) of NZEBs with VRF HP and HR systems. LCCA provides present values at a given study period, discounted payback period, and net-savings between VRF HP and HR systems in U.S. climate locations. Preliminary results indicate that the simulated VRF HP system can reasonably predict the energy performance of the actual VRF HP system and reduce between 15-45% for HVAC site energy uses when compared to a VAV system in U.S. climate locations. The VRF HR system can be used to lower building energy demand and thus achieve NZEB performance effectively in some hot and mild U.S. climate locations.