The objectives of the present work were to study the effects of irrigation with Agricultural Drainage Water (ADW) on lettuce (Lactuca sativa L.) yield, quality, and water use efficiency (WUE) with hydroponic system. Five mixing treatments of Agricultural drainage water (ADW) with fresh water (mean normal irrigation water) were used T1:(100% agricultural drainage water), T2:(75% agricultural drainage water mixed with 25% fresh water), T3:(50% agricultural drainage water mixed with 50% fresh water), T4:(25% agricultural drainage water mixed with 75% fresh water), and T5:( 100% fresh water). Nutrient Film Technique (NFT) hydroponic system was developed with five pipes PVC and nutrient solution added in rates: 12.5%, 25%, 50%, 75%, and 100% from standard nutrient solution for T1, T2, T3, T4, and T5, respectively. The results showed that lettuce plant can be produced in 50 days from planting to harvest by (NFT) hydroponic system. Moreover irrigation by using T3 had effectively increased the yields of green and dry matter. The higher Lettuce yields obtained with trend T3 > T5 > T2 > T4 > T1. And plants irrigated with T3 used water more efficiently than those irrigated with other water treatments. The higher water use efficiency (WUE) 39.96 kg/m3 was obtained with T3 and the lower value 16.67 with T1. On the other hand mineral nutrient contents in dry matter of N, P, K, and Ca contents were obviously higher in plants irrigated with T5 than with other water treatments. Heavy metals (Cd, Ni, Cr and Pb) contents in Lettuce shoots were higher in plants irrigated with T3 than those irrigated with other water treatments, but their levels did not reached the maximum allowed levels by FAO for edible crops.