Abstract Variable refrigerant flow (VRF) air conditioning system is widely used in commercial buildings for space cooling and heating. However, some VRF systems used in high-rise buildings cannot work efficiently or even stop working because of the relatively high ambient air temperature, caused by the thermal plume effect of exhaust heat from outdoor units. In this paper, the thermal plume air flow of the layer-based VRF systems is investigated through computational fluids dynamics (CFD) simulation. Moreover, an illustrative example of practical VRF system in a 30-storey office building in Shenzhen is analyzed to optimize the layout of the outdoor units. Preliminary results show that the exhaust heat of outdoor units can cause ascending thermal plume flow, leading to higher inlet temperatures for VRF air conditioners on upper floors, even exceeding the warning upper threshold value. It also indicates that enlarging the distance between outdoor units on different floors is an effective way to impair the thermal plume effect for VRF outdoor units and improve the thermal performance of the whole system. For the studied case, the average inlet temperatures can be decreased by 22% for VRF outdoor units with floor interval. This work can provide guidance for the optimization layout design of practical VRF air conditioning systems used in high-rise buildings.