When used to evaluate vaccination effectiveness, case-control studies are useful surrogates for controlled trials of vaccination programs. Their advantages over controlled trials are that 1) they involve relatively few participants, 2) the necessary information can be obtained within a short time, and 3) their results are based on actual field conditions. Their major and inescapable problem is producing convincing evidence that the vaccinated and unvaccinated populations are sufficiently alike in all relevant characteristics other than vaccination to allow a reasonable conclusion that vaccination effectiveness approximates vaccine efficacy. Even under uncontrolled circumstances, case-control studies should provide useful means of surveillance, indicating when some component of the vaccination program needs to be checked. Relative vaccine efficacy can be determined by case-control studies whenever the vaccine being used is the only factor in the vaccination program that has been changed.