Terahertz (THz) waves, positioned between microwave and infrared in the electromagnetic spectrum, have promising applications in medical imaging and biomedicine. In this study, terahertz irradiation at 2.52 THz (100 mW/cm2) did not alter the proliferation of human umbilical vein endothelial cells (HUVECs), but significantly enhanced their angiogenic capacity. This enhancement was accompanied by increased levels of angiogenesis-related proteins such as VEGF in the culture supernatant. ATAC sequencing and RNA sequencing revealed a significant increase in the expression of cytoskeleton-associated genes, including PDXP and SH3BP1, post-irradiation. Additionally, intracellular calcium concentration, closely linked to angiogenesis, markedly increased following terahertz exposure. However, diltiazem significantly mitigated the enhanced angiogenic capacity induced by terahertz irradiation. In conclusion, terahertz irradiation promotes angiogenesis in HUVECs, partly by activating the VEGF signaling pathway through increased calcium fluxes.