Nicotinic acid (NA, a.k.a. vitamin B3 or niacin) can reduce blood cholesterol and low-density lipoproteins whereas increase high-density lipoproteins. However, when NA is used to treat dyslipidemias, it causes a strong side effect of cutaneous vasodilation, commonly called flushing. A recent study showed that NA may cause flushing by lowering activation threshold temperature of the heat-sensitive capsaicin receptor TRPV1 ion channel, leading to its activation at body temperature. The finding calls into question whether NA might also interact with the homologous heat-sensitive TRPV2-4 channels, particularly given that TRPV3 and TRPV4 are abundantly expressed in keratinocytes of the skin where much of the flushing response occurs. We found that NA indeed potentiated TRPV3 while inhibited TRPV2 and TRPV4. Consistent with these gating effects, NA lowered the heat-activation threshold of TRPV3 but elevated that of TRPV4. We further found that activity of TRPV1 was substantially prolonged by extracellular NA, which may further enhance the direct activation effect. Consistent with the broad gating effect on TRPV1-4 channels, evidence from the present study hints that NA may share the same activation pathway as 2-aminoethoxydiphenyl borate (2-APB), a common agonist for these TRPV channels. These findings shed new light on the molecular mechanism underlying NA regulation of TRPV channels.