Background Anemia is the leading public health problem among pregnant women worldwide. Iron-Folic Acid (IFA) supplementation is the strategy to control pregnancy induced anemia, but its adherence status was not well studied. Objective The aim of this study was to assess the prevalence of IFA adherence and associated factors among pregnant women attending antenatal care at Denbiya district health centers. Methods Cross -sectional study design was conducted in Denbiya district health centers from April 2 to May 27, 2016. A total of 395 study participants were enrolled in the study. Systematic random sampling was used to select study participants. Data were collected using the interviewer-administered technique. Adherence to IFA supplementation was assessed by the pills count method. A logistic regression model was used. Results The study revealed that the prevalence of good adherence towards IFA supplementation among Antenatal care (ANC) service users’ at Denbiya district health centers were found to be 28.01% [95% CI, 24.01, 35.9]. Attending secondary school and above [Adjusted Odds Ratio (AOR) = 3.44, 95% CI: 1.09, 10.92], having two ANC visits [AOR = 2.53, 95% CI: 1.34, 4.76] and three and above ANC visits [AOR = 4.14, 95% CI: 2.14, 8.01] were significantly associated with good adherence of IFA supplementation. To the contrary, husband education status; secondary school and above reduced the odds of good adherence by 77% compared to illiterates to IFA supplementation [AOR = 0.23, 95% CI: 0.07, 0.72]. Conclusion The prevalence of good adherence among pregnant women towards IFA supplementation was low. Mothers’ education and having two or more ANC visits were positively associated with good adherence towards IFA supplementation.