Background: Malaria, a protozoan disease caused by the genus Plasmodium, is responsible for serious illnesses and death across the world. RTS, S/AS01 (Mosquirix™) is a recombinant protein-based malaria vaccine valuable for the prevention and control of the disease. However, studies done so far on the willingness to pay (WTP) malaria vaccine have been inadequate to inform policy-makers. Methods: A community-based cross-sectional study was conducted to assess the WTP for childhood malaria vaccine and associated factors among caregivers of under-five children from February to April 2019 in West Dembia district. A multistage stratified systematic sampling technique was used, and the contingent valuation method was used to estimate caregivers' willingness to pay for the vaccine. AOR with 95% CI and less than 0.05 p-values were used to declare factors associated with WTP. Results: Overall, 60.6% (95% CI: 56.60, 64.40%) of caregivers of under-five children were WTP for the childhood malaria vaccine at a price of US$ 23.11 per full doses. Urban residence (AOR=1.78, 95% CI: 1.04, 3.04), educational status (AOR=3.27; 95% CI: 1.07, 9.94) and vaccination experience for children (AOR= 2.12; 95% CI: 1.29, 3.48) were positively associated with the WTP. WTP for the vaccine was higher among rich households (AOR=3.15; 95% CI: 1.90, 5.22), caregivers who had the previous history of malaria attack (AOR=2.62; 95% CI: 1.68, 4.08), households with fewer members (AOR=1.59; 95% CI: 1.06, 2.40), and families more knowledgeable about malaria prevention and control (AOR=3.56; 95% CI: 1.83, 6.93) compared with their counterparts. Conclusion: The majority of the participants were WTP for the childhood malaria vaccine. A significant rise in willingness to purchase was observed at price below the profile price. Thus, it is of great value to policy-makers to understand the price sensitivity before setting the price of the vaccine.