This study analyzes the response of the Global Disasters Alerts and Coordination System (GDACS) in relation to a case study: the Kepulaunan Mentawai earthquake and related tsunami, which occurred on 25 October 2010. The GDACS, developed by the European Commission Joint Research Center, combines existing web-based disaster information management systems with the aim to alert the international community in case of major disasters. The tsunami simulation system is an integral part of the GDACS. In more detail, the study aims to assess the tsunami hazard on the Mentawai and Sumatra coasts: the tsunami heights and arrival times have been estimated employing three propagation models based on the long wave theory. The analysis was performed in three stages: (1) pre-calculated simulations by using the tsunami scenario database for that region, used by the GDACS system to estimate the alert level; (2) near-real-time simulated tsunami forecasts, automatically performed by the GDACS system whenever a new earthquake is detected by the seismological data providers; and (3) post-event tsunami calculations using GCMT (Global Centroid Moment Tensor) fault mechanism solutions proposed by US Geological Survey (USGS) for this event. The GDACS system estimates the alert level based on the first type of calculations and on that basis sends alert messages to its users; the second type of calculations is available within 30–40 min after the notification of the event but does not change the estimated alert level. The third type of calculations is performed to improve the initial estimations and to have a better understanding of the extent of the possible damage. The automatic alert level for the earthquake was given between Green and Orange Alert, which, in the logic of GDACS, means no need or moderate need of international humanitarian assistance; however, the earthquake generated 3 to 9 m tsunami run-up along southwestern coasts of the Pagai Islands where 431 people died. The post-event calculations indicated medium-high humanitarian impacts.