The living lab approach to building science research provides the ability to accurately monitor occupants and their environment and use the resulting data to evaluate the impact that various components of the built environment have on human comfort, health, and well-being. A hypothesized benefit of the living lab approach is the ability to simulate the real indoor environment in an experimentally controlled setting over relatively long periods of time, overcoming a significant hurdle encountered in many chamber-type experimental designs that rarely reflect typical indoor environments. Here, we present indoor environmental quality measurements from a network of sensors as well as building system design and operational data demonstrating the ability of a living lab to realistically simulate a wide range of environmental conditions in an office setting by varying air temperature, lighting, façade control, and sound masking in a series of three human subject experiments. The temporal variability of thermal and lighting conditions was assessed on an hourly basis and demonstrated the significant impact of façade design and control on desk-level measurements of both factors. Additional factors, such as desk layout and building system design (e.g., luminaires, speaker system), also contributed significantly to spatial variability in air temperature, lighting, and sound masking exposures, and this variability was reduced in latter experiments by optimizing desk layout and building system design. While ecologically valid experimental conditions are possible with a living lab, a compromise between realism and consistency in participant experience must often be found by, for example, using an atypical desk layout to reduce spatial variability in natural light exposure. Based on the experiences from these three studies, experimental design and environmental monitoring considerations for future office-based living lab experiments are explored.