Pack-off is a partially or complete blocking of the circulation flow in oil and gas drilling, which can lead to costly delays. Early detection and localization of a pack-off is crucial in order to take necessary actions avoiding downtime. This incident will affect physical friction parameters in the well. A model-based adaptive observer is used to estimate these friction parameters as well as flow rates. Detecting changes to these estimates can then be used for pack-off diagnosis, which due to measurement noise is done using statistical change detection. Isolation of incident type and location is done using a multivariate generalized likelihood ratio test, determining the change direction of the estimated mean values. The method is tested on simulated data from the commercial high-fidelity multi-phase simulator OLGA, where three different pack-offs at different locations and with different magnitudes are successfully detected at an early stage and with low false alarms.