During spray drying, dry powder is circulated into the nozzle zone to force collisions, inducing agglomeration. This study systematically determined the effect of fine powder mass flowrate (varying from 7.1–15.9 kg·h−1), drying air temperature (160–200 °C), and drying air mass flowrate (472.8–590.8 kg·h−1) on agglomerate size and morphology using a central-composite trial design. Agglomeration was quantified using an agglomeration index based on laser diffraction and by quantifying particle morphology using static image analysis. Response surface models were used to quantify factor effects. Increasing the fines mass flowrate had the largest positive effect on particle size enlargement and development of grape-like agglomerates. Increasing drying air temperature had a small negative effect on particle size enlargement and no significant effect on morphology. Increasing drying air mass flowrate had a small negative effect on particle size enlargement, but a positive effect on morphology. Finally, image analysis was found to be the preferred method to quantify the onset of agglomeration.