Genetic factors are known to have a role in determining susceptibility to infectious diseases 1, 2, although it is unclear whether they may also influence host efficiency in transmitting pathogens. We examine variants in HBB that have been shown to be protective against malaria 3 and test whether these are associated with the transmission of the parasite from the human host to the Anopheles vector. We conducted cross-sectional malariological surveys on 3,739 human subjects and transmission experiments involving 60 children and 6,446 mosquitoes in Burkina Faso, West Africa. Protective hemoglobins C (HbC, β6Glu→ Lys) 4, 5 and S (β6Glu→ Val) 6, 7, 8 are associated with a twofold in vivo (odds ratio 2.17, 95% CI 1.57–3.01, P= 1.0× 10− 6) and a fourfold ex vivo (odds ratio 4.12, 95% CI 1.90–9.29, P= 7.0× 10− 5) increase of parasite transmission from the human host to the Anopheles …