The increasing need to manage biosecurity threats, such as diseases, zoonoses, and biological weapons, poses serious challenges for risk analysts and policymakers. These threats are large in number, can occur concurrently, and may cause multiple tangible and intangible impacts. They often have an emerging nature, exacerbated by incomplete evidence about their probability of occurrence and potential impacts. There is also a limited amount of time and resources available to evaluate the risks posed by each threat, and it is difficult to learn from past projects. On the other hand, there is also a need to provide policymakers with transparent and consistent threat prioritizations, together with evidence-based recommendations. In response to these challenges, we propose a risk analysis framework for the prioritization and management of biosecurity threats. The framework encompasses key design choices that analysts may use in risk analysis projects along three dimensions: risk support, risk group, and risk organization. The framework has prescriptive value, as a design tool to inform risk analysis projects in this context, along with descriptive value, as a learning tool to understand past projects. We applied the framework prescriptively in two biosecurity threat prioritization projects for the UK Department for Environment, Food and Rural Affairs, and illustrate its descriptive value by reporting our experience of these projects as in-depth case studies. Overall, the proposed framework provides important insights into the impact of different design choices on the success of risk analysis projects for biosecurity threat prioritizations.