There remain few nationally representative studies of drinking water quality at the point of consumption in developing countries. This study aimed to examine factors associated with E. coli contamination in Ghana. It drew on a nationally representative household survey, the 2012−2013 Living Standards Survey 6, which incorporated a novel water quality module. E. coli contamination in 3096 point-of-consumption samples was examined using multinomial regression. Surface water use was the strongest risk factor for high E. coli contamination (relative risk ratio (RRR) = 32.3, p < 0.001), whilst packaged (sachet or bottled) water use had the greatest protective effect (RRR = 0.06, p < 0.001), compared to water piped to premises. E. coli contamination followed plausible patterns with digit preference (tendency to report values ending in zero) in bacteria counts. The analysis suggests packaged drinking water use provides some protection against point-of-consumption E. coli contamination and may therefore benefit public health. It also suggests viable water quality data can be collected alongside household surveys, but field protocols require further revision.