Recent challenges to public health regulation such as Indonesia’s challenge to the United States’ tobacco flavouring ban in the World Trade Organization (‘WTO’), and the WTO and investment treaty challenges to Australia’s plain tobacco packaging scheme, have raised common problems of evidence in the international trade and investment law regimes. Responding states are faced with high expectations in justifying their public health measures with empirical evidence connecting the measure with its purported health outcomes. This paper compares approaches to evidence in international trade and investment law and seeks to derive lessons for policymakers in developing public health regulation with potential trade and investment treaty challenges in mind. The paper reflects on the kinds of evidence needed to successfully defend such challenges and the appropriate approach to assessing such evidence in disputes in these two fora.