Summary: The inhalation performance of a Dry Powder Inhaler (DPI) are strictly correlated to the critical quality attributes (CQA) of the Active Pharmaceutical Ingredient (API). Particles typically need to be within the 1-5 µm aerodynamic diameter range in order to reach the airways . Such dimensions are usually targeted by means of micronization of the crystalline API. A widely used micronization equipment is the jet-mill apparatus in which micronization is achieved by air or nitrogen at very high pressure. The two main Critical Process Parameters (CPP) which directly affect the API particle size are the micronization pressure and the feed rate. This was demonstrated by a Principal Component Analysis (PCA) that took into consideration four of the main API CQAs affecting the DPI Fine Particle Fraction (FPF) (particle size distribution, particle specific surface area, Cohesion Adhesion Balance (CAB) and amorphous content), micronization pressure and feed rate. As a consequence, a direct correlation between DPI FPF with both API CQAs related to particle dimension (particle size distribution and specific surface area) and CPPs of the micronization process was observed. The two CPPs were studied by means of a Design of Experiment (DoE) approach to obtain a validated model able to directly predict the DPI FPF resulting from the formulation manufactured starting from the obtained micronized API. An equation correlating the DPI FPF with the micronization pressure and feed rate was obtained, demonstrating the possibility to modulate the desired DPI inhalation performance by directly controlling the micronization parameters.