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Background: Even though antenatal care (ANC) visits seems to be the key strategy to increase adherence to iron and folic acid supplements during pregnancy, the problem still remains unresolved. Therefore, this study planned to assess adherence to iron and folic acid supplements and associated factors among pregnant mothers attending ANC at Gulele sub-city Government Health Centers in Addis Ababa, Ethiopia, 2019. Methods: An institution-based cross-sectional study design was conducted on 403 pregnant women attending ANC at governmental health centers in Gulele sub city of Addis Ababa from May to June, 2019. The study participants were selected by systematic random sampling techniques, and an interviewer administered questionnaire was used to collect data. Descriptive statistics and logistic regression models were used to analyze the data. The results were considered statistically significant at p-value < 0.05. Results: The proportion of mother's adherent to iron and folic acid supplements was 62.3% with a 95% CI of 57.5– 67.0. Women who had no formal education (AOR=2.37; 95% CI=1.25– 4.51), poor knowledge about anemia (AOR=1.97; 95% CI=1.24– 3.13), developing any other health problem during current pregnancy (AOR=2.59; 95% CI=1.55– 4.32), attending health information about iron/folic acid supplement (AOR=2.06; 95% CI=1.08– 3.921 and forgetful (AOR=2.23; 95% CI=1.40– 3.56) mothers were more likely to be non-adherent to the supplement compared with their counterparts. Conclusion and Recommendation: The status of maternal adherence was medium compared with other studies, and maternal educational status, knowledge about anemia, exposure to information, experiencing of health problems, and forgetfulness were associated with adherence behavior. This indicates that improving dissemination of information about the supplements and designing a reminder mechanism was needed to improve the adherence status of mothers to the supplement. [ABSTRACT FROM AUTHOR]