Many studies have been carried out on using computational fluid dynamics (CFD) to explore spray-drying phenomena. However, due to the complexity of the drying process in a conventional spray dryer, including the wide droplet size distribution, complicated particle trajectory, and difficulty in taking online measurements, validation of the computational codes or the models remains a challenging task. In this study, experimental conditions employed in a more defined spray-drying condition, published recently on the spray drying of mono-disperse skim milk droplets in a vertical cylindrical chamber, are simulated using ANSYS FLUENT. We have examined the effects of droplet-dispersion patterns on the drying results and found ways to incorporate more practical shrinkage models into the code to make simulations more realistic. Through a comparison with the relevant experimental results on 10∼50 wt% skim milk published recently by the same group, we have identified a few areas that urgently need more detailed research. Using the revised sets of codes established here, we simulated skim milk droplets (with a uniform size between 180 μm to 220 μm) spray dried by 90°C to 180°C hot-air streams. The quantitative drying history data predicted by our new model would help ensure better understanding of the system.