Abstract This study aims to investigate quantitatively the direct correlation between the mechanical strength of powder agglomerates and their dispersion into aerosols by a dry powder inhaler. Agglomerates of mannitol as a model drug-only formulation were prepared by a rolling method followed by exposure to various relative humidity (RH: 55%, 82%, 86% and 90%). The agglomerate strength was obtained from the compression of single agglomerates at a selected speed rate using an Instron testing machine. The dispersion performance (FPF Loaded) was determined at flow rates of 60 and 100 l min −1 using an Aeroliser ® coupled to a multistage liquid impinger. Results showed an inverse linear relationship between the agglomerate strength and the dispersion performance. An increase in strength from 3 to 183 kPa resulted in a significant drop ( P<0.05) of 18% in the FPF Loaded. Agglomerates containing ‘solid bridges’ exhibited higher strength (three to eight times) and lower FPF (5–15%, corresponding to 86% and 90% RH) compared to those containing ‘liquid bridges’. These results have provided direct information on the agglomerate strength and its quantitative relationship with powder aerosol performance.