Small and wide angle high energy x-ray scattering experiments were performed upon cooling itraconazole from the melt to investigate the structural origin of the two transitions at ∼74°C and ∼90°C observed in DSC measurements. Slight changes to the main WAXS peak at Q=1.33±0.01Å−1 were observed at 90°C and are found to be inter-molecular in nature, suggesting a liquid to isotropic transition. This finding was supported by complementary wide angle neutron scattering measurements. For temperatures at and below ∼74°C two strong rings appear in the 2D-SAXS pattern at Q=0.24±0.01Å−1 and 0.43±0.01Å−1. The SAXS spectra were further deconvoluted into sharp and broad components. A narrowing of the broad component is associated with only minor changes in the packing arrangements of the itraconazole molecules below ∼90°C, while the appearance of the sharp component below ∼74°C is attributed to the formation of a polydomain lamellar phase.