This work aimed to optimize the production capacity of oyster mushroom (Pleurotus ostreatus), using as substrates vegetables residues: pine chips (Pinus sylvestris), eucalyptus chips (Eucalyptus globulus) and corn cob (Zea mays). For this the Simplex Centroid design (mixture design) was used, considering 10 treatments (0 - 100% of the three substrates). An ANOVA was applied to evaluate differences (p<0.05) among the treatments. As main results, pine chips increased the production capacity of oyster mushrooms and eucalyptus chips reduced it. By the desirability function of this methodology, the optimum mixture of substrates was found. This mixture should be made of 100% of pine chips, 0% of eucalyptus chips and %g of corn cob. Finally, a mathematical model was obtained (R2>0.98) which predicts the production capacity of oyster mushrooms using these three substrates.