To significantly increase the contribution of numerical computational fluid dynamics (CFD) simulation for risk assessment and decision making, it is important to quantitatively measure the impact of uncertainties to assess the reliability and robustness of the results. As unsteady high-fidelity CFD simulations are becoming the standard for industrial applications, reducing the number of required samples to perform sensitivity (SA) and uncertainty quantification (UQ) analysis is an actual engineering challenge. The novel approach presented in this paper is based on an efficient hybridization between the anchored-ANOVA and the POD/Kriging methods, which have already been used in CFD-UQ realistic applications, and the definition of best practices to achieve global accuracy. The anchored-ANOVA method is used to efficiently reduce the UQ dimension space, while the POD/Kriging is used to smooth and interpolate each anchored-ANOVA term. The main advantages of the proposed method are illustrated through four applications with increasing complexity, most of them based on Large-Eddy Simulation as a high-fidelity CFD tool: the turbulent channel flow, the flow around an isolated bluff-body, a pedestrian wind comfort study in a full scale urban area and an application to toxic gas dispersion in a full scale city area. The proposed c-APK method (anchored-ANOVA-POD/Kriging) inherits the advantages of each key element: interpolation through POD/Kriging precludes the use of quadrature schemes therefore allowing for a more flexible sampling strategy while the ANOVA decomposition allows for a better domain exploration. A comparison of the three methods is given for each application. In addition, the importance of adding flexibility to the control parameters and the choice of the quantity of interest (QoI) are discussed. As a result, global accuracy can be achieved with a reasonable number of samples allowing computationally expensive CFD-UQ analysis. (C) 2016 Elsevier Inc. All rights reserved.