BackgroundGhana adopted the 2012 World Health Organization (WHO) policy on intermittent preventive treatment of malaria in pregnancy (IPTp) and implemented it in 2014 in all regions of Ghana. Despite the implementation of this policy, there has been an unacceptably low percentage of eligible women receiving the optimal dose of IPTp in Ghana which leaves millions of pregnant women unprotected from malaria. The study, therefore, assessed the predictors of three or more doses (optimal dose) of sulfadoxine-pyrimethamine (SP) in Northern Ghana.MethodsA cross-sectional study was conducted among 1188 women in four selected health facilities in Northern Ghana from September 2016 to August 2017. Information on socio-demographic and obstetric characteristics reported SP use, and maternal and neonatal outcomes were collected which was double-checked from the maternal health book as well as the antenatal care register. Pearson chi-Square and ordered logistic regression were used to determine the predictors of reported optimal SP use.ResultsOut of the 1146 women, 42.4% received 3 or more doses of IPTp-SP as recommended by the national malaria control strategy. SP uptake was significantly associated with antenatal care (ANC) attendance (aOR 0.49, 95% CI 0.36–0.66, P < 0.001), primary education (aOR 0.70, 95% CI 0.52–0.95, P = 0.022), four or more antenatal care visits (aOR 1.65, 95% CI 1.11–2.45, P = 0.014), ANC care visit in second trimester (aOR 0.63, 95% CI 0.49–0.80, P < 0.001) and third trimester (aOR 0.38, 95% CI 0.19–0.75, P = 0.006) and malaria infection during late gestation (aOR 0.56, 95% CI 0.43–0.73, p < 0.001).ConclusionThe percentage of pregnant women who received three or more doses is below the target of the National Malaria Control Programme (NMCP). The push factors for the optimal use of SP are higher educational attainment, four or more ANC visits, and early initiation of ANC. The study also confirmed earlier findings that IPTp-SP uptake of three or more doses prevents malaria in pregnancy and improves birth weight. The uptake of IPTp-SP among expectant women will be informed and increased by encouraging formal general education beyond the primary level and encouraging early initiation of ANC visits.