Since the grinding and chemical reagents required for flotation are expensive, coarse particle flotation reduces grinding costs and makes the subsequent process more accessible and cheaper. Recent studies suggest that the flotation of coarse particles using microbubbles has some advantages. However, a thorough analysis of the effectiveness of various flotation parameters and the impact of their interactions on the recovery of coarse particles in the presence and absence of microbubbles has yet to be fully understood. In the current study, the two-level factorial and Box-Behnken experimental designs were performed to characterize, assess, and optimize the implications of seven numerical (sodium oleate, collector; calcium oxide, activator; MIBC, frother; impeller speed; froth depth; pulp concentration; fine particles) and one categorical (microbubbles) independent parameters on the coarse quartz particles. Characterization revealed that froth depth did not significantly affect the flotation recovery of coarse particles in the mechanical laboratory cell. The effects of the variables in the presence of microbubbles revealed that sodium oleate and impeller speed significantly impacted recovery, followed by calcium oxide and fine particles, both of which had a medium influence, and MIBC and pulp concentration, which had a minimal impact. The recovery of coarse particles increased by 92.714% when microbubbles were used, compared to the estimated maximum recovery under ideal conditions of 62.258% without them. From this, it can be concluded that a high coarse particle flotation recovery is possible by optimizing the hydrodynamic conditions and the chemical environment using microbubbles.