A study was conducted to evaluate effects of phytase and coccidial vaccine on growth performance, bone mineralization, nutrient digestibility, and intestinal gene expression of broiler chickens. The experiment was conducted in a 2 × 4 completely randomized factorial arrangement with 6 replicates per treatment and 10 birds each. Applications of coccidiosis vaccine and different dietary treatments were the 2 main factors in the current study. The dietary treatments included 1) a positive control (PC; 0.90% Ca and 0.45% available P: avP); 2) a negative control (NC; 0.75% Ca and 0.30% AvP); 3) NC + 500 FTU/kg of phytase (NC + 500PHY); and 4) NC + 1500 FTU/kg of phytase (NC + 1500PHY). Data were analyzed using SAS by 2-way ANOVA via GLM procedure. The statistical significance was set at P ≤ 0.05, and means were further separated using Tukey's Test. The results indicated that vaccination had no effect on growth performance except for feed intake from 0 to 14 d but negatively (P < 0.05) regulated bone ash and Ca digestibility. Birds fed with the Ca and P-reduced diet (NC) showed a lower BWG and bone ash compared to birds fed with the normal diet (PC), but supplementing phytase mitigated the negative effects on those birds. Broilers fed the NC diet had higher (P < 0.05) total Ca and P digestibility, and phytate degradation; supplementing phytase further increased P digestibility and phytate degradation of the broilers. A significant interaction (P < 0.05) between phytase and vaccination was observed, suggesting the vaccinated birds fed the PC diet and the unvaccinated birds fed the NC + 1500PHY increased calcium-sensing receptor gene expression compared with the unvaccinated birds fed the PC diet. In conclusion, in spite of coccidiosis vaccine, supplementing phytase at 1,500 FTU/kg alleviated the negative effects on growth performance, bone mineralization, and apparent ileal digestibility of P and phytate.