The development of fully reusable launch systems has been the topic of many studies since the 1960s. Over the years, several aspects of both so-called single- and two-stage-to-orbit space planes have provided many interesting research topics. Amongst others, the constrained trajectory optimisation has proven to be a challenging subject. In this chapter, an inverse-dynamics approach is combined with trajectory optimisation and analysis, by discretising a representative (vertical-plane) ascent trajectory into a number of flight segments, and by parametrising the guidance in terms of flight-path angle as a function of altitude. When the individual guidance parameters are varied, the effect on performance indices payload mass and integrated heat load can be analysed. This can subsequently lead to a refinement of the trajectory. To do so with limited effort, design-of-experiment techniques are used. It is shown that with this relatively simple simulation scheme, combined with variance analysis and response-surface methodology, the insight in the trajectory dynamics can be increased. Alternatively, this method can be used as refinement to an otherwise (local) optimum trajectory. It is stressed, though, that the application of design of experiments to the ascent-trajectory problem cannot replace numerical optimisation. Finally, the impact of using thrust-vector control as a means to (partially) trim the vehicle shows significant fuel savings and should therefore be included in the optimisation process.