In this study, the agronomic viability of oyster mushrooms [Pleurotus ostreatus (Jacq.) P. Kumm.] is studied by reusing spent mushroom substrates (SMS). For this purpose, SMS from Pleurotus ostreatus with commercial nutritional supplements (Calprozime®, Champfood® and Promycel®) as additives and with wheat straw, calcium sulphate and calcium carbonate at different doses has been evaluated. Physical and chemical characterization of the substrates, and quantitative production parameters have been evaluated in one growing season. The mixture of wheat straw (3,000 g) and SMS (3,000 g) supplemented with 120 g of each of the commercial supplements (Promycel®, Champfood® and Calprozime®) generated adequate substrates with an excellent unit weight of the fruiting bodies and acceptable biological efficiencies (near 50%). In the substrates with supplemented wheat straw, the biological efficiencies ranged from 65.60% to 73.28%. Consequently, the SMS from Pleurotus ostreatus could be a low-cost substrate with selective and balanced nutrients for growth and development of oyster mushrooms.