In order to minimize the health risks to agricultural workers, and consumers of wastewater irrigated produce, the World Health Organisation has developed guidelines for the safe use of wastewater in agriculture. This study sought to test the appropriateness of the current Quantitative Microbial Risk Assessment model and the multiple-barrier approach advocated by the WHO guidelines. Over a one year period, over 500 produce and ready-to-eat salad samples were collected from fields, markets, and kitchens in Accra, Ghana, and over 300 soil and irrigation water samples were collected. All samples were analysed for E. coli, human adenovirus and norovirus using standard microbiological procedures. In addition, almost 700 participants including farmers, food vendors, and consumers were interviewed and observed to assess critical exposures associated with the transmission of faecal pathogens. The results showed that irrigation water was significantly more contaminated than farm soil, though exposure to soil was found to pose the key risk to farmers due to hand-to-mouth events. Over 80% of produce samples were found contaminated with E. coli, with street food salad being the most contaminated (4.23 Log E. coli/g), and that consumption of salads did not meet health standards. Risk factors identified for produce contamination included farm soil contamination, wastewater use for irrigation, poor hygiene, and operating with a hygiene permit. Awareness of the source of irrigation water was low, but despite the high awareness of health risk, consumers did not prioritize health indicators when buying produce from vendors. Similarly, farmers’ awareness of health risk did not influence their adoption of safer farm practices. The study recommends the promotion of interventions that would result in more direct benefits to producers and vendors, together with hygiene education and inspection, hygiene certification and enforcement of food safety byelaws in order to increase the uptake of the multi-barrier approach.