The present study was conducted to determine the prevalence and factors associated with adherence to iron-folic acid supplementation (IFAS) among pregnant women in eastern Sudan. A cross-sectional survey was conducted among pregnant women who obtained antenatal care (ANC) at Gadarif Maternal Hospital in eastern Sudan between May 1 and August 31, 2023. Face-to-face interview questionnaires were used to gather sociodemographic, obstetric, and clinical data (age, parity, education, residence, and previous medical diseases). Knowledge of anemia and IFAS was assessed. Multivariate analysis was performed to adjust for confounders. A total of 568 pregnant women were enrolled in the present study. Among them, 449 (79.0%) adhered to the IFAS. The multivariate analysis showed that the adjusted odds ratio (AOR) of IFAS adherence increased with ANC visits > 4 (AOR = 1.68, 95.0% CI = 1.01-2.77) and knowledge of anemia (AOR = 2.06, 95.0% CI = 1.437-3.276). In the univariate analysis, maternal occupation and knowledge of IFAS adherence were the only factors associated with IFAS adherence. Maternal age, parity, gestational age, education, residence, occupation, medical insurance, medical disease, and husband's occupation were not associated with IFAS. Forgetfulness (71.0%), frustration from taking many drugs (54.6%), and unpleasant tests of the supplement (50.7%) were the main reasons for not taking the IFAS. About four out of five pregnant women adhered to the IFAS, indicating a good level of adherence, especially among women who attended more than four ANC visits and those with good knowledge of anemia. More attention is needed to encourage ANC to increase adherence to IFAS.