The lack of information related to the scaling-up of technologies used for preparing polymeric nanoparticles (NP) might hinder the introduction of these colloidal carriers into the pharmaceutical market. In the present study, the scale-up of ibuprofen-loaded NP produced by three manufacturing processes – salting-out, emulsification–diffusion and nanoprecipitation – was assessed at pilot-scale by increasing 20-fold the laboratory-batch volume from 60 ml to 1.5 l. Eudragit® L100-55 and poly(vinyl alcohol) (PVAL) were used as polymer and emulsifying agent, respectively. The influence of the hydrodynamic conditions on the NP characteristics such as mean size, drug content, residual PVAL and morphology was also investigated. At pilot-scale, stirring rates of 790–2000 rpm lead to NP mean sizes ranging from 557 to 174 nm for salting-out and from 562 to 230 nm for emulsification–diffusion. An increase in the stirring rate enhances the droplet break-up phenomenon which leads to the formation of finer emulsion droplets and thus smaller NP. Moreover, the influence of the stirring rate on the mean size of NP can be predicted using a model based on a simple power law. The continuous method used for nanoprecipitation scale-up allows production of NP in a reproducible way over a relatively short time. Finally, for the three methods, NP characteristics were reproduced well at both scales. However, the scale-up process induced a slight reduction in the size and drug loading of NP.