Epidemiology and modelling are currently under pressure to build consistent scenarios of control in case of deliberate release of biological weapons. In order to assess the key parameters for the control of a smallpox outbreak in a large city (2 million inhabitants), we built a stochastic model to simulate the course of an epidemic controlled by ring vaccination and case isolation. Assuming a reference scenario with 100 index cases and implementation of intervention 25 days after the attack, the model forecasts an epidemic of 730 cases with an epidemic duration of 240 days. Setting intervention 20 days later would result in an almost fourfold increase in the epidemic size. A multivariate sensitivity analysis has selected three key parameters: the basic reproduction number (i.e. the number of secondary cases infected by one case in an entirely susceptible population, equal to 3 in the reference scenario), time to intervention, and proportion of traced and vaccinated contacts.