The void fraction inside granules prepared by spray drying is an important factor influencing the strength, dissolution, and other properties of the granules. Void fraction is usually measured with a mercury porosimeter, but this requires elaborate operations and the equipment is not widely available. Moreover, this method is not suitable for broken granules, granules with surface holes, or weak granules. In this paper, a method to estimate the void fraction inside a granule was proposed on the basis of the measured size distribution of granules and the estimated size of initial droplets. It was found that the size distribution based on weight basis provided better results, since the number-based distribution yielded serious errors by ignoring small particles in estimating the size distribution of initial droplets. As a result, the median diameter on a weight basis was found useful to estimate the void fraction inside granules over a wide range from hollow to fully packed granules.