Nano-sizing offers a promising method for the formulation of poorly aqueous soluble compounds. Nanosuspensions can be prepared by top-down or bottom-up approaches. The different conditions encountered in these two approaches can greatly affect nanosuspension characteristics. In this study, milling via microfluidization and precipitation via sonication were compared to study their effects on the formation and stability of ibuprofen nanosuspensions. Various stabilizers (SLS, PVP K-30, Pluronic F-68 and F-127, Tween 80 and different hydroxypropyl methylcelluloses (HPMCs)) were evaluated. Both processes resulted in a similar trend in the initial particle size and comparable short-term physical stability of suspensions. Of all the stabilizers investigated, the HPMCs were the most effective both in terms of particle size reduction and short-term physical stability. Differences in stabilizer efficacy were observed between the two processing methods. The initial particle size of the suspensions prepared using microfluidization correlated with the solubility of ibuprofen in the respective stabilizer solutions. Whereas, the initial particle size of suspensions prepared using precipitation under sonication correlated with the HLB values of the stabilizers. The solubility of ibuprofen in the stabilizer solution also played a significant role in the increase in particle size on storage, indicating Ostwald ripening.