Background Since 2008, Indoor Residual Spraying (IRS) has been performed in Benin in 19 districts, including 4 in southern Benin, 9 in Atacora, and 8 in Atacora, Alibori and Donga in northern Benin.However, Benin still struggles with questions about IRS cost benefit and epidemiological impact. We discussed lessons learned and challenges from 10 years of IRS in Benin to be shared with the stakeholders involved in vector control implementation for decisions making.Methods We have assessed entomological parameters in IRS communes since 2008. In all IRS intervention communes, decreases in Human Biting Rate (HBR) of An. gambiae, blood feeding inhibition and Entomological Inoculation Rate (EIR) as compared to control district have been measured.Results EIR was reduced by 80-90%, which is encouraging, but should be observed with caution because: (i) the reduction may be insufficient to decrease epidemiological indicators given that the residual EIR in IRS districts is still higher than it is in some regions of stable malaria; (ii) the reduction in EIR is based on comparisons with control communes, but it is difficult to select control areas with the same environmental characteristics as intervention areas; (iii) despite the reduction, half of all mosquitoes that entered IRS-treated houses succeeded in taking human blood meals. Further, there are behaviors among Benin's population that limit IRS efficacy, including recent data showing that >90% of people are not protected by IRS between 7-10 PM. This is due to the fact that they remain outside and that most people are not protected from mosquito bites after 10 PM because they either sleep outside without IRS protection or inside without an ITN. Moreover, people have large amounts of clothing hanging on walls where mosquitoes can rest instead of IRS-treated walls. Finally, other components are important to consider in implementing IRS among which: (i) Vector resistance management strategies are sometimes poorly understood; this is actually different from replacing an insecticide by another after the emergence of resistance; (ii) African countries should prepare to finance IRS themselves.Conclusion To curtail residual malaria transmission, additional interventions able to target vectors escaping IRS should be prioritized.