In this study, we seek to explain a growing divergence between the US and EU regulatory policies over nanotechnology environmental, health, and safety risks. Faced with significant scientific and regulatory uncertainties, incremental approaches have been taken in both regulatory systems, but substantial differences are evident in terms of both policy processes and stringency. While the EU exhibits a regulatory integration process with stringent adjustments of existing legislative frameworks, the US is far less engaged in regulatory adaptations. We have carried out a comparative analysis of the EU and US regulatory policies. We suggest that literature perspectives that focus on differing public attitudes, economic interests, and advocacy pressure groups do not suffice to explain the regulatory policy divergence. We argue that a combined effect of domestic politics and policy styles provides the most powerful explanation of why the US and EU currently differ with respect to their regulatory responses to nanotechnology risks and uncertainties.