Antenatal anaemia is associated with increased peripartum transfusion requirement in South Africa. We studied whether HIV was associated with the response to treatment of iron-deficiency anaemia. Prospective cohort study. Hospital-based antenatal anaemia clinic in South Africa. Equal-sized cohorts of pregnant women testing positive for HIV (HIV+) and testing negative for HIV (HIV-) with iron-deficiency anaemia. Haemoglobin trajectories of women with confirmed iron-deficiency anaemia (ferritin<50ng/ml) were estimated from the initiation of iron supplementation using mixed-effects modelling, adjusted for baseline HIV status, ferritin level, maternal and gestational ages and time-varying iron supplementation. Haemoglobin trajectories. Of 469 women enrolled, 51% were HIV+, 90% of whom were on antiretroviral therapy (with a mean CD4+ lymphocyte count of 403cells/mm3 ). Anaemia diagnoses did not differ by HIV status. A total of 400 women with iron-deficiency anaemia were followed during treatment with oral or intravenous (6%) iron therapy. In multivariable analysis, haemoglobin recovery was 0.10g/dl per week slower on average in women who were HIV+ versus women who were HIV- (P=0.001), 0.01g/dl per week slower in women with higher baseline ferritin (P<0.001) and 0.06g/dl per week faster in women who were compliant with oral iron therapy (P=0.002). Compared with women who were HIV-, women who were HIV+ with iron-deficiency anaemia had slower but successful haemoglobin recovery with iron therapy. Earlier effective management of iron deficiency could reduce the incidence of peripartum blood transfusion. Among pregnant women with iron-deficiency anaemia in South Africa, HIV slows haemoglobin recovery in response to oral iron therapy.