Mechanical flotation cells remain the dominant flotation technology in the mineral processing industry, but they are typically optimised for intermediate particle sizes (10–100 µm) and perform poorly when treating coarse particles. Poor coarse particle recovery is attributed to inadequate solids suspension, increased turbulence-induced bubble-particle detachment, and reduced froth recovery. Improving coarse particle flotation therefore requires effective suspension at reduced power input, together with a stable pulp-froth interface and appropriate control of bubble size and gas dispersion. However, no systematic investigation has evaluated the combined effects of cell design and operating variables on these hydrodynamic responses. Pilot-scale testing was conducted in a 1 m3 mechanical flotation cell. A Design of Experiments approach was used to evaluate the effects of rotor diameter, impeller off-bottom clearance, baffling configuration, superficial gas velocity (Jg), and solids concentration. Suspension was assessed using the critical impeller speed for complete offbottom suspension (Njs), while specific power draw, bubble size, gas dispersion, and pulp-froth interface oscillations were measured at this condition. A large rotor operated with baffles at low clearance, reduced solids concentration, and low airflow rate improved suspension and decreased power draw. However, this configuration also deteriorated gas dispersion and increased interface oscillations. Regression modelling and multi-response optimisation were therefore used to balance these competing responses, identifying an optimal configuration comprising a large rotor-stator system operated at low clearance and intermediate air rate. Relative to the standard configuration, this arrangement enhanced suspension, reduced power draw and interface oscillations, whilst maintaining adequate gas dispersion. These readily retrofittable design and operating modifications have strong potential to improve coarse particle recovery. Future work will test this hypothesis through direct flotation experiments.