BACKGROUND: The World Health Organization (WHO) and UNICEF recommend that HIV-positive women should avoid all breastfeeding only if replacement feeding is acceptable, feasible, affordable, sustainable and safe. Little is known about the effectiveness of the implementation of these guidelines in developing country settings. OBJECTIVE: To identify criteria to guide appropriate infant-feeding choices and to assess the effect of inappropriate choices on infant HIV-free survival. METHOD: Prospective cohort study of 635 HIV-positive mother-infant pairs across three sites in South Africa to assess mother to child transmission of HIV. Semistructured questionnaires were used during home visits between the antenatal period and 36 weeks after delivery to collect data concerning appropriateness of infant feeding choices based on the WHO/UNICEF recommendations. RESULTS: Three criteria were found to be associated with improved infant HIV-free survival amongst women choosing to formula feed: piped water; electricity, gas or paraffin for fuel; and disclosing HIV status. Using these criteria as a measure of appropriateness of choice: 95 of 311 women who met the criteria (30.5%) chose to breastfeed and 195 of 289 women who did not meet the criteria (67.4%) chose to formula feed. Infants of women who chose to formula feed without fulfilling these three criteria had the highest risk of HIV transmission/death (hazard ratio, 3.63; 95% confidence interval, 1.48-8.89). CONCLUSIONS: Within operational settings, the WHO/UNICEF guidelines were not being implemented effectively, leading to inappropriate infant-feeding choices and consequent lower infant HIV-free survival. Counselling of mothers should include an assessment of individual and environmental criteria to support appropriate infant-feeding choices.