An effective optimization design approach which combines CFD modeling and the Taguchi DOE method is presented for immobilized photocatalytic annular reactors used for water treatment. The analyzed reactor design incorporated the use of repeated ribs for improving the external mass transfer to the TiO2-coated wall. The CFD model was experimentally evaluated using 2,4-D as a model pollutant, providing close predictions of the photocatalytic degradation performance of the photoreactors over a wide range of Reynolds numbers (300 < Re < 10 000). The statistical analysis showed that the performance of the studied annular photocatalytic reactors was improved up to 60% using the ribs. A comparison of different reactor design factors indicated that better performance can be obtained using small outer tube diameters, large inner/outer tube diameter ratios, large (rib height)/(hydraulic diameter) ratio, and small (rib pitch)/(rib height) ratios. In addition, it was concluded that the (rib height)/(hydraulic diameter) ratio was the design parameter having the greatest impact (57%) on photoreactor performance.