In the present study, the cross contamination and distribution of Escherichia coli O157:H7 was investigated in fresh-cut lettuce by simulating a commercial process at a pilot plant scale with different initial inoculum levels. A deterministic approach was used to derive a potential Food Safety Objective (FSO) for the studied pathogen. The experimental outcomes, together with literature data, were used to develop a probabilistic exposure model for E. coli O157:H7 to elucidate potential risk management metrics, i.e., Performance Objectives (POs) and a Performance Criterion (PC) at specific process steps within the food chain of fresh-cut leafy vegetables. The proposed FSO was estimated to be −6.0 log CFU/g for E. coli O157:H7 at consumption. The experimental results indicated that the pathogen could cross contaminate most of the samples in a lot at the different contamination levels tested (1-7 log CFU/g) resulting in a homogeneous distribution of E. coli O157:H7 in fresh-cut lettuce after processing. Based on the modelling results, the average concentration estimated as PO in unprocessed lettuce should be −5.8 log CFU/g to meet the proposed FSO. On the other hand, the PO established after washing and packaging (processed lettuce) showed a lower value, with −6.8 log CFU/g E. coli O157:H7. Reduction levels during the washing or disinfection step estimated as the PC should be > 2.9 log CFU/g. The establishment of PC for the washing step, assisted by the use of disinfection process indicators (e.g., generic E. coli), could be considered as a suitable measure to reach the FSO in fresh-cut leafy vegetables. The suggested POs and PC would help food businesses and authorities to establish safety targets and corrective actions to reduce the number of potentially contaminated lettuce lots on the market, thus reducing the number of E. coli O157:H7 infections. •The washing step resulted in homogenous contamination by E. coli O157:H7 in processed fresh-cut lettuce.•A novel model-based approach proposed to derive risk management metrics.•The estimated Food Safety Objective for E. coli O157:H7 was −6.0 log CFU/g.•Reduction levels > 2.9 log CFU/g E. coli O157:H7 in fresh-cut vegetables should be achieved during the washing step.