ABSTRACT Syphilis in pregnancy has remained a significant reproductive and public health problem globally with high prevalence reported in the resource-poor countries of sub-Saharan Africa. Syphilis pregnant has adverse effects on both the mother, pregnancy, unborn foetus and the child, if at all the pregnancy is carried to term. Other than sexual activity being the key risk factor for contracting syphilis, other factors exist that do increase the chances of getting the infection. Data on the prevalence and associated factors of syphilis in Uganda’s general population, leave alone among pregnant women, is scanty. It is non-existent in Kiryandongo District and so this study set out to assess the prevalence and factors associated with syphilis among pregnant women attending ANC at Kiryandongo General Hospital. A 6-month’s descriptive study that involved a total of 4,067 pregnant mothers attending ANC, 1,317 (32.38%) on their maiden visit, and with 2,453 (60.32%) being tested for syphilis and 2 (0.08%) of then testing positive for syphilis. The factors associated with syphilis in pregnancy were rural residence (odds: 0.00083), low socioeconomic status, low maternal age with low education, HIV seropositivity with a positive STI history.