This article synthetizes observations from five experiments and reports on the effects of timing and intensity of defoliation on the white and red Vitis vinifera cultivars Pinot noir, Gamay, Merlot, Chasselas, and Doral. Intensive defoliation (removal of six basal leaves + six lateral shoots per shoot) was completed at three developmental stages of the grapevine: preflowering, flowering, and bunch closure. Preflowering defoliation had tremendous consequences on vine agronomic performance, mainly to the detriment of berry set; the yield was highly affected by preflowering defoliation (approximately -35% of that from vines with no defoliation). The intensity of defoliation allowed its impact on the yield to be modulated. The intensity of defoliation also had a positive impact against millerandage, sunburn symptoms, and Botrytis cinerea development. The berry skin thickness doubled and the polyphenol concentration increased significantly with preflowering defoliation. Due to preflowering defoliation, the red wines were often preferred for their color and mouthfeel. However, this practice had a negligible impact on white wine composition. Regardless, preflowering defoliation did not negatively impact wine parameters. In the context of this study, preflowering defoliation has potential to reduce vigor and control high production potential. Preflowering defoliation also represents a prophylactic solution to reduce both chemical applications and cluster-thinning costs.