Abstract: The application of X-ray powder diffraction (XRPD) combined with pair-wise distribution function (PDF) in detecting miscibility in amorphous polymer systems has been demonstrated.1 Here, a matching PDF between linearly combined (theoretical) PDF for the pure components and measured PDF suggests that the sample is immiscible; dissimilar PDF profiles indicates the system is miscible. However, interpretation of overlaid PDF data can be subjective. The objective of this study is to demonstrate the feasibility of using principal component analysis (PCA) to analyse XRPD-PDF data to detect miscibility in freeze dried amorphous-amorphous systems. Polyvinylpyrrolidone 30k (PVP30), PVP 90k (PVP90), dextran 10k (DEX10), polyvinyl alcohol (PVA) and trehalose dihydrate (TREH) were used as received. Formulations (A) PVP30-DEX10, (B) PVP30-PVA and (C) PVP90-TREH at various ratios were prepared and freeze dried below the collapse temperature. All samples were characterised and analysed using XRPD, PDF, PCA and validated by differential scanning calorimetry. Previously it has been reported that PVP30-DEX10 is immiscible, while PVP30-PVA and PVP90-TREH are miscible systems. In our PDF plots, subtle characteristic changes could be observed between theoretical and measured data. However interpreting PDF changes was subjective and is limited to one-to-one comparison. When XRPD-PDF analysis is combined with PCA, comparison of multiple PDF profiles with superior clarity on the subtle changes was achieved. Overall, PCA plots effectively distinguished systems that are immiscible or miscible. XRPD-PDF analysis combined with PCA can be used as an alternative tool to screen and detect miscibility of binary amorphous formulations.