The power draw and emulsification performance of in-line rotor-stator mixers were investigated experimentally and theoretically, to predict droplet size as a function of process and formulation variables and to establish scale-up rules. The effect of process conditions, three mixer scales and thirteen rotor-stator geometry configurations on emulsification performance were investigated. Emulsions of a wide range of silicone oil viscosities of varying phase volumes, dispersed in aqueous surfactant and non-surfactant solutions were studied. For lab to factory scale in-line rotor-stator mixers, the most appropriate scaling parameter for mean drop size was tip speed at constant residence time for single and multiple passes. At a single scale, the stator open area was the rotor-stator geometry parameter which had the greatest effect on power draw and emulsification in turbulent flow. Mean drop size was a strong function of the rotor speed, dispersed phase viscosity, interfacial tension, and less dependent upon the mixer flow rate, continuous phase viscosity and dispersed phase volume fraction (for surfactant systems). Correlation of mean drop size with energy dissipation rate indicated that droplet break-up mainly depends on turbulent inertial stresses. Energy dissipation rate profiles were calculated theoretically using numerical simulations to calculate power draw and to solve population balance model equations. This is the first study in open literature where power consumption and drop size distributions in three scales of in-line rotor-stator mixer are reported.