Hospitals are controlled yet complex ecosystems which provide a therapeutic environment that promotes healing, wellbeing and work efficiency for patients and staff. As these buildings accommodate the sick and vulnerable, occupant wellbeing and good indoor environmental quality (IEQ) that deals with indoor air quality (IAQ), thermal comfort, lighting and acoustics are important objectives. As the specialist nature of hospital function demands highly controlled indoor environments, this makes them energy intensive buildings due to the complex and varying specifications for their functions and operations. This paper reports on a holistic building performance evaluation covering aspects of indoor air quality, thermal comfort, lighting, acoustics, and energy use. It assesses the performance issues and inter-relationships between IEQ and energy in a new building on a hospital campus in the city of Bristol, United Kingdom. The empirical evidence collated from this case study and the feedback received from the hospital staff help identify the endemic issues and constraints related to hospital buildings, such as the need for robust ventilation strategies in hospitals in urban areas that mitigate the effect of indoor and outdoor air pollution and ensuring the use of planned new low-carbon technologies. Whilst the existing guidelines for building design provide useful instructions for the protection of hospital buildings against ingress of particulate matter from outdoors, more advanced filtration strategies may be required to enact chemical reactions required to control the concentration levels of pollutants such as nitrogen dioxide and benzene. Further lessons for improved performance in operation and maintenance of hospitals are highlighted. These include ensuring that the increasingly available metering and monitoring data in new buildings, through building management systems, is used for efficient and optimal building operations for better IEQ and energy management. Overall, the study highlights the need for an integrated and holistic approach to building performance to ensure that healthy environments are provided while energy efficiency targets are met.