Abstract A capillary penetration technique was used to determine the wettability of morphine sulfate powders by a range of wetting and partially wetting liquids. Wetting rates were found to be dependent on both the properties of the wetting liquid and the morphine sulfate batch. A number of liquids were established as perfectly wetting, and the critical surface tension for morphine sulfate wetting was estimated to be ∼40 mN m −1. Effective capillary radii for packed beds of morphine sulfate powders were determined in the range 0.3–0.6 μm; these are compared with particle size, shape and surface area data. From the Washburn approach, the advancing water-particle contact angles for the different morphine sulfate samples were determined to be in the range 57–79°, with errors less than ±3°. Sessile drop measurements on the same samples were unable to determine reproducible equilibrium contact angles and could not differentiate between the batches. The role of surface chemistry, crystal morphology and crystal structure in controlling morphine sulfate powder wettability was explored by X-ray photoelectron spectroscopy (XPS), scanning electron microscopy (SEM) and X-ray diffraction. Contact angles were shown to correlate with both the aspect ratio of the morphine sulfate crystals and the nitrogen-to-oxygen surface atomic concentration ratio, determined by SEM and XPS, respectively. The relative exposure of different crystal faces is considered to play an important role in controlling the wettability of morphine sulfate powders.