Abstract A study was conducted to evaluate the efficacy of biosynthetic 6-phytase depending on basal diet composition on growth performance and bone mineralization in weaned piglets. A total of 192 male weaned piglets with initial body weight (BW) of 8.47 ± 0.70 kg (at 33 d of age), distributed in a randomized block design with a 3 x 2 factorial arrangement of treatments. Three basal diet compositions (BD1: adequate in energy and nutrients with phytic P (PP) = 0.23%; BD2 = BD1 minus 70 kcal NE/kg, 0.15% points similarly in digestible P (dig.P) and calcium (Ca) with PP = 0.23%; and BD3 = BD1 minus 70 kcal NE/kg, 0.15% points similarly in dig.P and Ca with PP = 0.29%) and two phytase inclusion (Rovabio PhyPlus; 0 or 1,000 FTU/kg diet) were used in this experiment. The corn-soybean meal-based diets were fed into 2 phases: post-weaning 1 and 2 from 1 to 14 and 15 to 42 d, respectively. Body weight and feed intake were measured at the end of each phase, and average daily gain (ADG), average daily feed intake (ADFI) and feed to gain ratio (F:G) were calculated for the whole experimental period. At the end of the study, all piglets from 16 pens per treatment (n = 32 piglets/treatment) were euthanized and the metacarpi bones were collected for bone ash and P content determinations. There were significant interactions (P < 0.05) between basal diet composition and phytase inclusion on final BW, ADG, F:G, ash and P contents in metacarpal bones of piglets. Compared with unsupplemented diet, the addition of phytase in both nutrient-reduced diets improved final BW, ADG, F:G, ash and P contents in bones, while no improvements (P > 0.05) were observed on these parameters by phytase supplementation in adequate-nutrient diet. There was no significant interaction (P > 0.05) between basal diet composition and phytase inclusion on ADFI. Reduction in nutrients without (BD2) or with increasing dietary PP level (BD3) decreased (P = 0.004) ADFI, compared with adequate-nutrient diet. However, addition of biosynthetic 6-phytase improved (P = 0.03) ADFI by 5.3% compared with unsupplemented diets. The results of the present study highlight that adding biosynthetic 6-phytase to low energy and nutrient diets was more effective compared with the effects in an adequate-nutrient diet in weaned piglets.