The annular frictional performance of non-Newtonian fluids is among the major considerations during development of hydraulic programs for drilling operations. Proper estimation of the frictional pressure losses become more critical when determining hydraulic horsepower requirements and selecting proper mud pump systems to foresee any serious problems that might occur with hydraulics during drilling operations. Because the theological behaviour of the non-Newtonian fluids is known to be challenging, it becomes even more complicated during pipe rotation, especially in eccentric wellbores. In many cases, significant differences are observed when theoretical calculations and measurements for pressure losses are compared. This study aims to develop correction factors for determining the frictional pressure losses accurately in eccentric horizontal annulus for non-Newtonian fluid, including the effect of pipe rotation. Extensive experimental work has been conducted on METU-PETE Flow Loop for numerous non-Newtonian drilling fluids, including KCI-polymer muds and PAC systems for different flow rates and pipe rotation speeds, and frictional pressure losses are recorded during each test. Rheological characteristics of the drilling fluids are determined using a rotational viscometer. Observations showed that pipe rotation has a significant influence on frictional pressure loss, especially at lower flow rates. Up to a point, as the pipe rotation increases, the frictional pressure losses also increase. As the flow rates are increased, the effect of pipe rotation on frictional pressure losses diminishes. Also, after a certain pipe rotation speed, no additional contribution of pipe rotation on frictional pressure loss is observed. When the developed friction factors are used, there is a good agreement between the calculated and observed frictional pressure losses for any pipe rotation speed.