Significance MicroRNAs can repress target genes to regulate cellular function in vivo. The miR-17∼92 cluster is critical for cell cycle control, survival signaling, and angiogenesis, but the individual components of the cluster and their endogenous roles in vivo are less well understood. Here we show that the loss of endothelial-derived miR-17∼92 increases basal cardiac and limb arteriogenesis and improves ischemia-induced changes in blood flow. One component of the cluster, miR-19, directly targets FZD4 and LRP6, thereby regulating WNT signaling in vitro and in vivo, and antagonism of miR-19 up-regulates WNT signaling and improves defective blood flow recovery.