Fast-growing hybrid aspens (Populus tremula L. x P. tremuloides Michx.) are currently of great interest in Sweden since they can produce biomass at high rates and, at the same time, can be used to produce higher value wood products. This study focuses on the effects of pruning hybrid aspen to improve its wood quality. About 50% of the trees in the experimental stand were pruned by removing twigs, at heights up to 4 m, when they were 7–8 years old. Ten years later, 20 pruned and 20 unpruned trees, representing four clones, were randomly selected. Ten knots or twig/stem junctions, respectively, per tree were exposed for inspection using a chain saw and examined. The results revealed that pruned trees cicatrised the knots within about three years and thereafter produced substantial amounts of faultless wood. In contrast, unpruned trees (which had retained almost 80% of their twigs, often as dry twigs with bark pockets) had produced small uneven amounts of quality wood. Removal of twigs with acute angles and/or large diameters resulted in greater colour defects and rot in annual rings outside the pruning position, but the time of cicatrisation was not significantly affected. The results show that pruning can be used to enhance the wood quality of hybrid aspen over a short time period, and that pruning should be performed early during the rotation period when branches are small, in order to minimize discolouration and rot in the new annual rings.