The interest in using electrospraying as a manufacturing method for amorphous solid dispersions has grown remarkably. However, the impact of formulation and process parameters needs further clarification. In this study, amorphous solid dispersions of darunavir and hydroxypropyl methylcellulose (HPMC), hydroxypropyl methylcellulose acetate succinate (HPMC AS) and polyvinylpyrrolidone K-30 (PVP) were prepared with electrospraying and spray drying, in order to compare both solvent based manufacturing techniques. Our results revealed that electrospraying was as successful as spray drying. The formulations prepared with the two methods were amorphous and had similar characteristics concerning the residual solvent and drug release. Although differences in the morphology and the particle size distributions were observed, this was not reflected in the pharmaceutical performance of the formulations. Electrosprayed amorphous solid dispersions made up of darunavir and PVP were studied in more detail by means of a full factorial experimental design. The impact of two process and two formulation parameters on the properties of the amorphous solid dispersions was determined. The feed flow rate had a significant effect on the diameter and morphology of the particles whereas the tip-to-collector distance had no significant impact within the tested range. The drug loading influenced the homogeneity and the residual solvent, and the total solids concentration had an impact on the homogeneity and the morphology.