With the on- and off-road diesel engine emission regulations getting more stringent across the world, diesel aftertreatment systems are expected to deliver outstanding performance and reliability. These objectives should be met by fulfilling tight packaging constraints and incurring only modest material and testing costs. A major strategy for meeting these often conflicting requirements is the effective use of simulation tools such as computational fluid dynamics (CFD) in system design and performance evaluation. Prerequisites for using this CFD analysis-led-design approach, however, are knowledge of the confidence level of the predictions and knowledge of the appropriate transfer functions that establish the relationships between the measured performance parameters and model predictions. The primary aim of the present work is to develop statistically and physically relevant measures that assess the uniformity of flow in aftertreatment systems. Most commonly, a flow distribution index based on L1 norm has been used for quantifying flow uniformity. The index proposed in the present work is based on the L2 norm thereby making it more sensitive to flow maldistribution. Key statistical advantages of the proposed index are first discussed. Then, CFD predictions of flow velocities and indices are compared with experimental measurements made under realistic flow and measurement location conditions for various geometries and flow rates. Main sources of uncertainties in measurements and predictions are identified and discussed. Discussions on the use of L2 norm based indices in assessing exhaust gas species and temperature uniformity are also provided.