The methodology to perform bioequivalence studies for prodrug products has not been finalized by FDA leaving the investigators to speculate over the proper approach. This study innovatively utilized the bootstrap methods for testing in vivo bioequivalence on both parent drug and metabolite of four prodrug products: Clopidogrel, Prednisone, Allopurinol, and Mycophenolate Mofeil. Monte Carlo simulation was employed to generate in vivo plasma concentration time profiles of prodrug products in Matlab. The bootstrap methods provided confidence intervals that were more accurate and sensitive compared to traditional parametric methods. The bootstrap methods were also used to construct confidence intervals of the similarity factor f2 for in vitro bioequivalence testing of four prodrug products. Bootstrap confidence intervals of f2 furnished clearer evidence that was more crucial for assessment of in vitro similarity of prodrug products than the single measurement of similarity factor f2. In vitro/in vivo Correlation (IVIVC) was assessed for both parent drug and metabolite of the selected prodrug products by Gastroplus. IVIVC of Clopidogrel and Prednisone appeared to show stronger relationship compared to that of Allopurinol and Mycophenolate Mofeil. More formulation data is required for conclusive validation of the correlation.