Prenatal iron and folic acid (IFA) supplements are offered free to all pregnant women in Malawi to reduce maternal anemia and improve birth outcomes. We investigated the association between self-reported compliance to IFA intake and risk of low birth weight (LBW). Pregnant women who attended Bwaila Maternity Wing of Lilongwe District Hospital for delivery were recruited (n = 220). We used a questionnaire to collect self-reported information on IFA use and maternal sociodemographic data. Before delivery, blood samples for maternal hemoglobin (Hb) and folate status, and upon delivery, birth weight, and other newborn anthropometrics were measured. We used multivariable logistic regression to determine risk of LBW by prenatal IFA intake. The self-reported number of IFA pills taken during pregnancy was positively associated with Hb, but not serum and RBC folate concentration: <45, 45–89 and ≥90 pills taken corresponded with mean (SD) Hb 10.7 (1.6), 11.3 (1.8), and 11.7 (1.6) g/dL, respectively (p = 0.006). The prevalence of LBW was 20.1%, 13.5% and 5.6% for those who reported taking IFA pills 60 IFA pills reduced risk of LBW delivery (OR (95% CI) = 0.15 (0.03–0.70), p = 0.033) than taking ≤30 pills. Self-reported compliance to IFA use is valid for assessing prenatal supplement program in Malawi, especially Hb status, and can reduce the rate of LBW.