This study assessed the contamination of Escherichia coli, in lettuce grown with treated domestic wastewater in four different irrigation configurations: open spray, spray under plastic sheet cover, open drip and drip under plastic sheet cover. Samples of lettuce from each irrigation configuration and irrigating wastewater were collected during the growing season. No E. coli was detected in lettuce from drip irrigated beds. All lettuce samples from spray beds were positive for E. coli, however, no statistical difference (p > 0.05) was detected between lettuces grown in open spray or covered spray beds. The results from the field experiment were also compared to a laboratory experiment which used submersion of lettuce in wastewater of known E. coli concentration as a surrogate method to assess contamination following irrigation. The microbial quality of spray bed lettuces was not significantly different from submersed lettuce when irrigated with wastewater containing 1,299.7 E. coli MPN/100 mL (p > 0.05). This study is significant since it is the first to validate that the microbial contamination of lettuce irrigated with wastewater in the field is comparable with a laboratory technique frequently applied in the quantitative microbial risk assessment of the consumption of wastewater irrigated salad crops.