Background: Progress in controlling malaria has stalled in recent years. Today the malaria burden is increasingly concentrated in a few countries, including Burkina Faso, where malaria is not declining. We carried out a cohort study to identify risk factors for malaria infection in children in south-west Burkina Faso, an area with high insecticide-treated net (ITN) coverage and insecticide-resistant vectors.Methods: Incidence of malaria infection was measured in 252 children aged 5 to 15 years, using active and passive detection, during the 2017 transmission season, following clearance of infection. Demographic, socioeconomic, environmental and entomological risk factors, including use of ITNs and insecticide resistance were monitored. Results: During the six-month follow-up period, the overall incidence of Plasmodium falciparum infection, was 2.78 episodes per child (95% CI= 2.66-2.91) by microscopy, and 3.11 (95% CI= 2.95-3.28) by PCR. The entomological inoculation rate (EIR) was 80.4 infective bites per child over the six-month malaria transmission season. At baseline, 80.6% of children were reported as sleeping under an ITN the previous night, although at the last survey, 23.3% of nets were in poor condition and considered no longer protective. No association was found between the rate of P. falciparum infection and either EIR (Incidence Rate Ratio, IRR: 1.00, 95% CI: 1.00–1.00, p=0.08) or mortality in WHO tube tests when vectors were exposed to 0.05% deltamethrin (IRR: 1.05, 95% CI: 0.73–1.50, p=0.79). Travel history (IRR: 1.52, 95% CI: 1.45–1.59, p<0.001) and increasing socio-economic status were associated with an increased risk of P. falciparum infection (IRR: 1.05, 95% CI: 1.00–1.11, p=0.04).Conclusions: Malaria infection incidence remains overwhelmingly high in the study area. Our findings suggest that because of the exceptionally high levels of malaria transmission in the study area, malaria elimination cannot be achieved solely by mass deployment of ITNs and additional control measures are needed.