Objectives The objective of this study was to assess intervention strategies against a novel influenza epidemic through simulations of various scenarios in Sapporo city, Hokkaido, Japan. A series of interventions were examined: administration of antiviral drugs by two approaches [targeted antiviral prophylaxis (TAP) and school-age targeted antiviral prophylaxis (STAP)], school closure, restraint, and combinations of these four interventions. Methods In order to generate a more realistic situation, we constructed an individual-based model (IBM) for the transmission of influenza in which each individual was assigned personal information on the basis of the National Census and Employment Status Survey of Sapporo city. In addition, data on high-risk casual contact groups commuting in crowded trains and buses were obtained from a census on transportation modes and introduced into the model. Observational data from previous pandemics were used for the epidemiological parameters. Results Both TAP and STAP interventions were highly effective in suppressing the spread of infection during the early period of an outbreak, but STAP was inferior to TAP in terms of the ripple effect of the administration of antiviral drugs. School closure and restraint were able to bring about a delay in the peak of infection. The combination of TAP, school closure, and restraint interventions were highly effective in decreasing the total number of patients and shortening the epidemic period. Conclusions Based on the simulation results, we recommend implementing TAP together with both school closure and restraint as strategies against a future novel influenza outbreak. © 2010 The Japanese Society for Hygiene.