Vitis vinifera (variety Tempranillo) grapes were subjected to high hydrostatic pressure (HHP) treatments of 200, 400 and 550 MPa for 10 min, and its effect on microbial populations, phenol extraction and wine quality was examined. At ≥400 MPa, the wild yeast population was strongly reduced from 104 to <10 cfu/ml. Bacteria showed greater resistance, and a residual load remained even after the treatment at 550 MPa. The extraction of phenolic compounds from the HHP-treated grapes was improved, with higher concentrations of total phenols obtained compared to crushing alone. Anthocyanin extraction was also increased, producing wines with better colour intensity. These wines also had higher methanol and ethanol contents and returned higher aromatic quality and colour scores. The HHP treatment of grapes may assist in the use of yeast starters, increase phenol extraction from grape skins and improve wine quality.