This study was carried out at Soilless Culture Unit, Agric Faculty., Mansoura Univ., Egypt, from 2018 to 2020, to study the impact of three substrate culture systems (PVC pipes 4" in diameter with circular holes, slit PVC pipes 4" and slit PVC pipes 8") in A shape units and three growing media (peat moss, vermiculite and peat moss:vermiculite 1:1, v/v) and their interactions on growth and productivity of lattuga lettuce cv. Green Star grown soilless cultured. The experiment was designed as strip-plot design. The obtained results showed that, all studied traits as parameters of growth (plant height, foliage diameter/plant and leaves number and area/plant), yield (foliage and leaves fresh weights/plant and yield/unit) and leaves chemical composition (chlorophylls, N, P, K, …) significantly affected by all tested factors and their interactions. Concerning effect of substrate culture system, PVC pipes 4" with holes achieved the best significant means for all traits as compared to slit PVC pipes 8". Regarding influence of growing media, the mixture of peat and vermiculite gave the best significant values for all traits compared to vermiculite only. Respecting impact of combination treatments, the interaction treatment of PVC pipes 4" with circular holes+peat and vermiculite mixture had significant impacts on all forecited traits as compared to interaction one between slit PVC pipes 8"+vermiculite. Hence, it could be recommended that soilless culture of lettuce in PVC pipes 4" with holes+mixture of peat and vermiculite in A shape units is the best choice to achieve maximum growth and productivity of lettuce.