This study assessed the perception of pregnant women on indoor residual spraying (IRS), documented acceptability, and factors that significantly dictate willingness to use IRS among the pregnant women attending antenatal clinic in Ibadan Nigeria. A structured questionnaire was used to obtain relevant information from 500 pregnant women. Descriptive and principal component analysis (PCA) were done at 5% level of significance. Majority of the pregnant women had between good and fair knowledge of IRS. Less than 70% of the respondents were willing to allow IRS in their homes. Our PCA revealed that major factors responsible for acceptance and willingness to use IRS were associated with perceived benefits, advantages, and disadvantages of IRS rather than overall knowledge of IRS among the respondents. The analysis revealed that these factors were responsible for at least 80% of the reasons for a pregnant woman to willingly accept IRS or not. The factors that positively influenced willingness to use IRS include its benefit in controlling mosquitoes and other insects, reducing malaria incidence, and prolonged effects of IRS which is an added advantage over continuous purchase of aerosols. One major factor that may negatively affect the acceptance of IRS is the fact that you may have to pack out of the house and wait for more than 3 d before entering. This current study has identified some specific factors that seem to promote and/or reduce willingness to accept IRS as a malaria control intervention among pregnant women in South Western Nigeria.