Despite the profusion of promising new vaccines against illnesses prevalent in developing countries, uncertainties about the balance between costs and benefits of new vaccines have retarded their use in public health practice. Conventional prelicensure trials of vaccine protection exacerbate these uncertainties by focusing on measurement of vaccine efficacy--the performance of a vaccine under idealized conditions. Vaccine effectiveness trials provide a more pragmatic perspective by addressing the performance of a vaccine under the ordinary conditions of a public health program, by capturing direct as well as indirect effects of vaccination, and by comprehensively addressing outcomes of public health concern. The use of effectiveness trials should enable more rational triaging of new vaccines for developing countries and may accelerate the introduction of new vaccines into public health practice by resolving speculative debates about practical costs and benefits.