Numerical simulations of transport and isotope fractionation provide a method to quantitatively interpret vadose zone pore water stable isotope depth profiles based on soil properties, climatic conditions, and infiltration. We incorporate the temperature-dependent equilibration of stable isotopic species between water and water vapor, and their differing diffusive transport properties into the thermodynamic database of the reactive transport code TOUGHREACT. These simulations are used to illustrate the evolution of stable isotope profiles in semiarid regions where recharge during wet seasons disturbs the drying profile traditionally associated with vadose zone pore waters. Alternating wet and dry seasons lead to annual fluctuations in moisture content, capillary pressure, and stable isotope compositions in the vadose zone. Periodic infiltration models capture the effects of seasonal increases in precipitation and predict stable isotope profiles that are distinct from those observed under drying (zero infiltration) conditions. After infiltration, evaporation causes a shift to higher δ18O and δD values, which are preserved in the deeper pore waters. The magnitude of the isotopic composition shift preserved in deep vadose zone pore waters varies inversely with the rate of infiltration.