This study aims to investigate the role of impact angles on the de-agglomeration performance of powders for inhalation. Agglomerates of a model drug mannitol were impacted at customized impaction throats containing two angles (15-75 degrees and 45-45 degrees) or a single angle (15 degrees, 45 degrees and 90 degrees) using various air flow rates. The mass fraction of fine particles <5microm in the aerosol (FPF(Loaded)) was measured by a liquid impinger coupled to a laser diffractometer. Results showed that for the two-angle throats, there existed an optimal angle (45 degrees) and air flow (120lmin(-1)) for the FPF(Loaded), resulting from a balance between improved de-agglomeration and enhanced throat deposition with increasing air flow. When the throat contained two equal angles of 45 degrees , most powder deposition occurred at the first angle, indicating that the first angle was likely to cause major de-agglomeration, while the second angle might act as a facilitator for further break-up, but the deposition was minimum as the fragment sizes and velocity at the second impaction were smaller. This hypothesis was supported by further studies using single-angle throats and numerical simulation (DEM-CFD). These findings imply the potential importance of using angular design features for multiple impactions to improve DPI performance.