Addressing diseases of a high burden with the most cost-effective interventions could do much to reduce disease in the population. We conducted a cost-effectiveness analysis of 40 health interventions in Guinea, a low-income country in sub-Saharan Africa, using local data. Interventions were selected from treatment protocols at health centres, first referral hospitals and national programmes in Guinea, based upon consultation with health care providers and government plans. For each intervention, we calculated the costs (comprising labour, drugs, supplies, equipment, and overhead) in relation to years of life saved, discounted at 3%. The results show that the per capita costs and effectiveness of any intervention vary considerably. Average costs show no clear pattern by level of care, but effectiveness is generally highest for curative hospital interventions. Several interventions have a cost-effectiveness of US$100 per year of life saved (LYS) or less, and address more than 5% of total years of life lost. These include health centre interventions such as: treatment of childhood pneumonia ($3/LYS); rehydration therapy for diarrhoea ($7/LYS); integrated management of childhood pneumonia, malaria and diarrhoea ($8/LYS); short-course treatment of tuberculosis ($12/LYS); treatment of childhood malaria ($13/LYS), and childhood vaccination ($25/LYS). Outreach programmes for impregnated bed nets against malaria cost $43/LYS. Maternal and perinatal diseases, have slightly less cost-effective interventions: integrated family planning, prenatal and delivery care at health centres ($109/LYS) or outreach programmes to provide prenatal and delivery care ($283/LYS). A minimum package of health services would cost approximately $13 per capita, and would address a large proportion (69%) of major causes of premature mortality. This minimum package would cost about three times the current public spending on health, suggesting that health spending needs to rise to achieve good health outcomes.