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Describe the process of enacting and defending strong tobacco packaging and labelling regulations in Uruguay amid Philip Morris International’s (PMI) legal threats and challenges.Triangulated government legislation, news sources and interviews with policy-makers and health advocates in Uruguay.In 2008 and 2009, the Uruguayan government enacted at the time the world’s largest pictorial health warning labels (80% of front and back of package) and prohibited different packaging or presentations for cigarettes sold under a given brand. PMI threatened to sue Uruguay in international courts if these policies were implemented. The Vazquez administration maintained the regulations, but a week prior to President Vazquez’s successor, President Mujica, took office on 1 March 2010 PMI announced its intention to file an investment arbitration dispute against Uruguay in the International Centre for the Settlement of Investment Disputes. Initially, the Mujica administration announced it would weaken the regulations to avoid litigation. In response, local public health groups in Uruguay enlisted former President Vazquez and international health groups and served as brokers to develop a collaboration with the Mujica administration to defend the regulations. This united front between the Uruguayan government and the transnational tobacco control network paid off when Uruguay defeated PMI’s investment dispute in July 2016.To replicate Uruguay’s success, other countries need to recognise that strong political support, an actively engaged local civil society and financial and technical support are important factors in overcoming tobacco industry’s legal threats to defend strong public health regulations.