Objective— In resistance arteries, there is an emerging view that smooth muscle Ca V 3.2 channels restrain arterial constriction through a feedback response involving the large-conductance Ca 2+ -activated K + channel (BK Ca ). Here, we used wild-type and Ca V 3.2 knockout (Ca V 3.2 −/− ) mice to definitively test whether Ca V 3.2 moderates myogenic tone in mesenteric arteries via the Ca V 3.2-ryanodine receptor-BK Ca axis and whether this regulatory mechanism influences blood pressure regulation. Approach and Results— Using pressurized vessel myography, Ca V 3.2 −/− mesenteric arteries displayed enhanced myogenic constriction to pressure but similar K + -induced vasoconstriction compared with wild-type C57BL/6 arteries. Electrophysiological and myography experiments subsequently confirmed the inability of micromolar Ni 2+ , a Ca V 3.2 blocker, to either constrict arteries or suppress T-type currents in Ca V 3.2 −/− smooth muscle cells. The frequency of BK Ca -induced spontaneous transient outward K + currents dropped in wild-type but not in knockout arterial smooth muscle cells upon the pharmacological suppression of Ca V 3.2 channel. Line scan analysis performed on en face arteries loaded with Fluo-4 revealed the presence of Ca 2+ sparks in all arteries, with the subsequent application of Ni 2+ only affecting wild-type arteries. Although Ca V 3.2 channel moderated myogenic constriction of resistance arteries, the blood pressure measurements of Ca V 3.2 −/− and wild-type animals were similar. Conclusions— Overall, our findings establish a negative feedback mechanism of the myogenic response in which Ca V 3.2 channel modulates downstream ryanodine receptor-BK Ca to hyperpolarize and relax arteries.