ELTD1 is an orphan member of the adhesion-G-protein-coupled receptor family that is widely expressed in the microvasculature, frequently up-regulated in tumor vessels and has recently been suggested as a target for anti-angiogenic therapy. Here, we have evaluated the role of ELTD1 in developmental and tumor angiogenesis. ELTD1-/- mice were viable, fertile and born at normal mendelian ratios. Retinal angiogenesis and blood vessel formation in liver, kidney and lung was similar in wild-type and ELTD1-/- mice. Consistent with this, siRNA-mediated knockdown ELTD1 did not affect sprouting angiogenesis in vitro. Tumor growth of orthotopic GL261 tumors and subcutaneous T241 fibrosarcomas was increased in ELTD1-/- mice, while B16 melanoma and MB49 carcinomas implanted subcutaneously grew equally well in ELTD1-/- and wild-type mice. Importantly, vascular density was not affected by ELTD1-deficiency in any tumor model. Vascular leakage and T-cell infiltration were reduced in ELTD1-/- T241 tumors while no differences were detected in GL261 tumors. Taken together, our results show that ELTD1 is dispensable for vascular development and tumor angiogenesis and that targeting ELTD1 pharmacologically may results in enhanced tumor growth.