Reducing building energy demand plays a vital role in addressing the depletion of energy resources and energy-related environmental issues. Previous research identified the statistical correlations between embodied energy and costs of buildings. However, little research has explored the relationship between operational energy and life cycle cost performance of buildings. This paper aims to investigate the energy efficiency and cost effectiveness of energy saving measures (ESMs) and thereby identify the relationship between operational energy and life cycle cost performance of high-rise office buildings. Five types of ESMs with 32 scenarios were examined using a real-life 35-storey office building in Hong Kong as a typical high-rise high-density city. The five types of ESMs are (1) increase temperature setpoint, (2) adopt daylighting sensors and light-emitting diode lamps (3) replace with low-e glass, (4) upgrade heating, ventilation and air conditioning system, and (5) implement on-site renewable energy. The results discover a U-curve relationship between operational energy saving and initial investment cost of the five ESMs. Moreover, the results show a significant linear correlation between operational energy saving and net present value of the ESMs. Such relationship reveals trade-off and synergy effects largely existing between opertional energy and cost performance in improving energy efficiency of high-rise offic buildings. This research suggests that increasing indoor temperature setpoint should be prioritised in lowering operational energy. The results are discussed drawing on the findings of previous studies in other city contexts. This research contributes a novel life cycle perspective to future systematic research into building energy and economics. The findings are important to building designers in their decision-making of reducing buildings’ operational energy use in a cost-effective way.