The “soilless” cultivation of blueberry (Vaccinium corymbosum L.) in containers with peat as substrate allows overcoming the problem of unsuitable soils, thus enhancing the spread of this crop in new areas. Since the use of peat presents several critical environmental and economic sustainability issues, the evaluation of alternative solutions is required. The effectiveness of compost produced with solid digestate and residues from the vine-wine chain to replace part of the peat was therefore tested. Micropropagated plants of cultivar Duke grown in three substrates consisting of a mixture of commercial peat with three compost fractions (10, 20, 40%) were compared with plants grown in 100% unfertilized or fertilized peat (0.3 g of Osmocote per pot). Plant height did not significantly differ between the five theses at the end of the trial, whereas the total number of nodes per plant was higher than in the control theses, due to a greater development of secondary shoots. The nutritional status of the plants, monitored with Dualex, during the growing season, was generally not significantly different in the innovative substrates compared to peat alone. In mid-summer the plants grown in substrates with compost showed the best nitrogen balance index (NBI values). Plants cultivated with medium-high percentages of compost (20–40%) showed a lower degree of defoliation at the end of the trial, dependent on a slower decline of vegetative activity. The final destructive measures of fresh and dry weight of biomass and of its partitioning between roots and shoots highlight that the use of compost did not negatively affect the production of biomass, but rather, in the theses with the highest percentages of compost (20–40%), root development was stimulated.