In 2012, London hosted the Olympic and Paralympic Games (the Games), with events occurring throughout the United Kingdom (UK) between 27 July and 9 September 2012. Public health surveillance was performed by the Health Protection Agency (HPA). Collaboration between the HPA and the European Centre for Disease Prevention and Control (ECDC) was established for the detection and assessment of significant infectious disease events (SIDEs) occurring outside the UK during the time of the Games. Additionally, ECDC undertook an internal prioritisation exercise to facilitate ECDC’s decisions on which SIDEs should have preferentially enhanced monitoring through epidemic intelligence activities for detection and reporting in daily surveillance in the European Union (EU). A team of ECDC experts evaluated potential public health risks to the Games, selecting and prioritising SIDEs for event-based surveillance with regard to their potential for importation to the Games, occurrence during the Games or export to the EU/European Economic Area from the Games. The team opted for a multilevel approach including comprehensive disease selection, development and use of a qualitative matrix scoring system and a Delphi method for disease prioritisation. The experts selected 71 infectious diseases to enter the prioritisation exercise of which 27 were considered as priority for epidemic intelligence activities by ECDC for the EU for the Games.