Using Demographic and Health Survey datasets from Ghana and Nigeria, this study examined whether the protective effects of breast-feeding are greatest where the poorest sanitation conditions prevail. It was found that mixed-fed infants aged between 0 and 11 months tend to have a higher risk of diarrhoea than fully breast-fed children, while the risk of diarrhoea among weaned infants is twice that of mixed-fed infants. The probit regression models employed in the analysis were used to predict the probability of diarrhoea associated with each breast-feeding pattern for both ‘poor’ and ‘good’ sanitation areas. It was found that the risk of diarrhoea among mixed-fed infants in the poor sanitation areas tends to be high while the same risk among fully breast-fed infants tends to be minimal. In essence, the health risks of mixed feeding are real, particularly for infants aged less than 7 months, and are even worse for those weaned before 6 months of age.