The pursuit of the Millennium Development Goals and advancing the 'global health agenda' demand the achievement of health impact at scale through efficient investments. We have previously offered that sustainability-a necessary condition for successful expansion of programmes-can be addressed in practical terms. Based on benchmarks from actual child survival projects, we assess the expected impact of translating pro-sustainability choices into investment strategies. We review the experience of Save the Children US in Guinea in terms of investment, approach to sustainability and impact. It offers three benchmarks for impact: Entry project (21 lives saved of children under age five per US$100 000), Expansion project (37 LS/US$100k), and Continuation project (100 LS/US$100k). Extrapolating this experience, we model the impact of a traditional investment scenario against a pro-sustainability scenario and compare the deaths averted per dollar spent over five project cycles. The impact per dollar spent on a pro-sustainability strategy is 3.4 times that of a traditional one over the long run (range from 2.2 to 5.7 times in a sensitivity analysis). This large efficiency differential between two investment approaches offers a testable hypothesis for large-scale/long-term studies. The 'bang for the buck' of health programmes could be greatly increased by following a pro-sustainability investment strategy.