Abstract. Polynomial approximations of computationally intensive models are central to uncertainty quantification. This paper describes an adaptive method for non-intrusive pseudospectral approximation, based on Smolyak's algorithm with generalized sparse grids. We rigorously analyze and extend the non-adaptive method proposed in [6], and compare it to a common alternative approach for using sparse grids to construct polynomial approximations, direct quadrature. Analysis of direct quadrature shows that O(1) errors are an intrinsic property of some configurations of the method, as a consequence of internal aliasing. We provide precise conditions, based on the chosen polynomial basis and quadrature rules, under which this aliasing error occurs. We then establish theoretical results on the accuracy of Smolyak pseudospectral approximation, and show that the Smolyak approximation avoids internal aliasing and makes far more effective use of sparse function evaluations. These results are applicable to broad choices of quadrature rule and generalized sparse grids. Exploiting this flexibility, we introduce a greedy heuristic for adaptive refinement of the pseudospectral approximation. We numerically demonstrate convergence of the algorithm on the Genz test functions, and illustrate the accuracy and efficiency of the adaptive approach on a realistic chemical kinetics problem.Key words. Smolyak algorithms, sparse grids, orthogonal polynomials, pseudospectral approximation, approximation theory, uncertainty quantification AMS subject classifications. 41A10, 41A63, 47A80, 65D15, 65D321. Introduction. A central issue in the field of uncertainty quantification is understanding the response of a model to random inputs. When model evaluations are computationally intensive, techniques for approximating the model response in an efficient manner are essential. Approximations may be used to evaluate moments or the probability distribution of a model's outputs, or to evaluate sensitivities of model outputs with respect to the inputs [21,41,33]. Approximations may also be viewed as surrogate models to be used in optimization [22] or inference [23], replacing the full model entirely.Often one is faced with black box models that can only be evaluated at designated input points. We will focus on constructing multivariate polynomial approximations of the inputoutput relationship generated by such a model; these approximations offer fast convergence for smooth functions and are widely used. One common strategy for constructing a polynomial approximation is interpolation, where interpolants are conveniently represented in Lagrange form [1,42]. Another strategy is projection, particularly orthogonal projection with respect to some inner product. The results of such a projection are conveniently represented with the corresponding family of orthogonal polynomials [4,21,43]. When the inner product is chosen according to the input probability measure, this construction is known as the (finite dimensional) polynomial chaos expansion (PCE) [14,32,...