Objectives: Monitoring iron supplementation effectiveness in the affected populations is important in assuring its success. The research objective of this study is to evaluate the effectiveness of iron supplementation and its related factors in increasing the hemoglobin levels of women with anemia that reside in the area of Teluk Bintuni Regency in West Papua Province, Indonesia. Materials and Methods: A quasi-experimental study was performed to determine the changes in hemoglobin levels and the adherence between two supplementation groups (before and after supplementation). From the initial screening of hemoglobin levels of 875 reproductive-age women, 110 women with moderate and severe anemia were enrolled for a month-long iron supplementation therapy. This study was conducted from September 2018 until November 2019 at Teluk Bintuni Regency, West Papua, Indonesia. The changes in hemoglobin levels were measured after 30 days of iron supplementation. The associated factors, including participants’ characteristics, chronic energy deficiency (CED) levels, adherence to supplementation programs, and knowledge of anemia, were also assessed. The adherence level to the supplementation was measured using the Medication Adherence Rating Scale (MARS) questionnaires and the pill counting method. Results: The mean hemoglobin level significantly increased from 9.12±1.70 before supplementation to 10.15±1.65 after 30 days (P<0.001). Interestingly, results from the MARS questionnaires and pill counting method suggested that only 76% and 66% of participants adhered to the supplementation program, respectively. Further univariate analysis showed that adherence, ethnicity, and type of supplementation were factors that may influence the success of the iron supplementation therapy. Conclusions: Based on this study findings, it can be concluded that anemia is related to various factors, and its implementation should be carefully monitored, not solely depending on individual adherence.