This paper proposes a methodology to calibrate multizone airflow models in existing buildings. The methodology has been demonstrated with the widely used multi-zone model CONTAM and applied to two buildings, one synthetic and one actual. The methodology builds on previous workwith thecalibration process enhanced by the use of carbon dioxide tracer gas test data. A key concept highlighted in this paper is that calibration of airflow models is a highly over-parameterized problem and that some form of model reduction is imperative. This is achieved by performing an airflow-based sensitivity analysis to identify influential system drivers, a tracer gasbased sensitivity analysis to identify macro-zones (i.e. groups of rooms that can be combined into one zone for the purposes of predicting or studying dynamic airflow behavior under different types of stimuli), and finally, a process of tuning the model parameters. It is found that for mechanically ventilated commercial buildings, calibrating multi-zone models by reconciling differences between measured and predicted tracer gas behavior is more strongly impacted by those factors which significantly influence room air change rates than by airflow path leakage parameter tuning.