Aims: A growing number of foodborne illnesses has been associated with the consumption of fresh produce. In this study, the probability of lettuce contamination with Escherichia coli O157:H7 from manure-amended soil and the effect of intervention strategies was determined. Methods and Results: Pathogen prevalence and densities were modelled probabilistically through the primary production chain of lettuce (manure, manure-amended soil and lettuce). The model estimated an average of 0.34 contaminated heads per hectare. A minimum manure storage time of 30 days and a minimum fertilization-to-planting interval of 60 days was most successful in reducing the risk. Some specific organic farming practices concerning manure and soil management were found to be risk reducing. Conclusions: Certain specific organic farming practices reduced the likelihood of contamination. This cannot be generalized to organic production as a whole. However, the conclusion is relevant for areas like the Netherlands where there is high use of manure in both organic and conventional vegetable production. Significance and Impact of the Study: Recent vegetable-associated disease outbreaks stress the importance of a safe vegetable production chain. The present study contributed to this by providing a first estimate of the likelihood of lettuce contamination with E. coli O157:H7 and the effectiveness of risk mitigation strategies.