The Na+/Ca2+ exchanger (NCX) is considered to be involved in endothelial nitric oxide (NO) production and endothelium-dependent vasorelaxation, but little is known about the physiological and pathological roles of endothelial NCX in these processes. We examined the role of NCX1 in neovascularization in mice with hindlimb ischemia. Unilateral hindlimb ischemia was induced surgically in wild-type and heterozygous NCX1 knockout mice (NCX1+/−) mice. We found that in NCX1+/− mice, blood flow recovery was significantly augmented compared with that in wild-type mice. NG-nitro-L-arginine methyl ester treatment eliminated enhanced angiogenesis observed in NCX1+/− mice. These results suggest that NCX1 is involved in eNOS-dependent angiogenesis.