Recently a metallic state was discovered at the interface between insulating oxides, most notably LaAlO 3 and SrTiO 3 . Properties of this two-dimensional electron gas (2DEG) have attracted significant interest due to its potential applications in nanoelectronics. Control over this carrier density and mobility of the 2DEG is essential for applications of these unique systems, and may be achieved by epitaxial strain. However, despite the rich nature of strain effects on oxide materials properties, such as ferroelectricity, magnetism, and superconductivity, the relationship between the strain and electrical properties of the 2DEG at the LaAlO 3 ∕SrTiO 3 heterointerface remains largely unexplored. Here, we use different lattice constant single-crystal substrates to produce LaAlO 3 ∕SrTiO 3 interfaces with controlled levels of biaxial epitaxial strain. We have found that tensile-strained SrTiO 3 destroys the conducting 2DEG, while compressively strained SrTiO 3 retains the 2DEG, but with a carrier concentration reduced in comparison to the unstrained LaAlO 3 ∕SrTiO 3 interface. We have also found that the critical LaAlO 3 overlayer thickness for 2DEG formation increases with SrTiO 3 compressive strain. Our first-principles calculations suggest that a strain-induced electric polarization in the SrTiO 3 layer is responsible for this behavior. The polarization is directed away from the interface and hence creates a negative polarization charge opposing that of the polar LaAlO 3 layer. This behavior both increases the critical thickness of the LaAlO 3 layer, and reduces carrier concentration above the critical thickness, in agreement with our experimental results. Our findings suggest that epitaxial strain can be used to tailor 2DEGs properties of the LaAlO 3 ∕SrTiO 3 heterointerface.oxide interface | electronic transport | polar discontinuity S train has been used to engineer and enhance numerous properties of materials. For example, mobility in semiconductors (1,2), and transition temperatures in ferroelectric materials (3-6), and superconductors (7) have been controlled by strain. A recently discovered two-dimensional electron gas (2DEG) at the LaAlO 3 ∕SrTiO 3 interface (8,9) has attracted great interest due to its unique application to nanoscale oxide devices (10). So far, most studies of 2DEGs at oxide interfaces were performed using TiO 2 -terminated SrTiO 3 bulk single-crystal substrates. Despite the rich nature of strain effects on oxide materials properties, the relationship between the strain and electrical properties of the 2DEG at the LaAlO 3 ∕SrTiO 3 heterointerface remains largely unexplored.One important effect of strain arises from the constraint that integrating 2DEGs to other functional devices or substrates always involves strain. Understanding the effect of strain on a 2DEG at the LaAlO 3 ∕SrTiO 3 interface is essential for these considerations. In addition, incorporation of strain might lead to unique functional properties. For example, strain can induce an electric polarization in otherwise nonpol...