Weakly basic compounds which have pH dependent solubility are liable to exhibit pH dependent absorption. In some cases, a subtle change in gastric pH can significantly modulate the plasma concentration of the drug and can lead to sub-therapeutic exposure of the drug. Evaluating the risk of pH dependent absorption and potential drug-drug interaction with pH modulators are important aspects of drug discovery and development. In order to assess the risk around the extent of decrease in the systemic exposure of drugs co-administered with pH modulators in the clinic, a pH effect study is carried out, typically in higher species, mostly dog. The major limitation of a higher species pH effect study is the resource and material requirement to assess this risk. Hence, these studies are mostly restricted to promising or advanced leads. In our current work, we have used in vitro aqueous solubility, in silico simulations using GastroPlus™ and an in vivo rat pHeffect model to provide a qualitative assessment of the pH dependent absorption liability. Here, we evaluate ketoconazole and atazanavir with different pH dependent solubility profiles and based on in vitro, in silico and in vivo results, a different extent of gastric pH effect on absorption is predicted. The prediction is in alignment with higher species and human pH effect study results. This in vitro, in silico and in vivo(IVISIV) correlation is then extended to assess pH absorption mitigation strategy. The IVISIV predicts pH dependent absorption for BMS-582949 whereas its solubility enhancing prodrug, BMS-751324 is predicted to mitigate this liability. Overall, the material requirement for this assessment is substantially low which makes this approach more practical to screen multiple compounds during lead optimization.