The Comet Interceptor mission will attempt to fly by a yet undetermined target comet. The conditions of this flyby will remain largely unknown up to the selection of target and possibly even the moment of encounter. A detailed trajectory design phase, which includes verification of the technical limitations implied by the flyby geometry, precedes target comet selection, so the flyby velocity and the details of the geometry are known in advance. Solar irradiance and the neutral gas expansion speed can be estimated reasonably well. However, the comet outgassing rate, the dust production rate, and the solar wind conditions are only known within broader uncertainty margins. The present contribution aims to optimally choose the distance of closest approach based on a simplified formalism that expresses, on one hand, the science return to be expected as a function of the closest approach distance, and, on the other hand, the risks implied by a close approach. This is done by performing Monte Carlo simulations over a large sample of possible flyby configurations, based on the expected probability distributions of the gas and dust production rates and the solar wind conditions, and for different closest approach distances. For small flyby distances, a spacecraft can study the nucleus, the neutral gas coma, and the induced magnetosphere from up close, benefiting the science return. There is a trade-off to be made against the cometary dust collision risk, which becomes larger close to the nucleus. The change of the optimal flyby distance with gas and dust production rate, solar EUV flux, and flyby speed is discussed. The conclusion is that the Comet Interceptor main spacecraft and its two daughter probes – within the limitations of the approximations made – would benefit from a target comet with a gas production rate of 1028-1029 molecules·s-1, a low dust-to-gas ratio, a high solar EUV flux, and a slow flyby speed (De Keyser et al., 2024, https://doi.org/10.1016/j.pss.2024.106032), for which the optimal closest approach distance (somewhere between 300 to 2000 km for the mother spacecraft) would yield a good science return at a limited risk.