Linear gradient programs are very frequently used in reversed phase liquid chromatography to enhance the selectivity compared to isocratic separations. Multi-linear gradient programs on the other hand are only scarcely used, despite their intrinsically larger separation power. Because the gradient-conformity of the latest generation of instruments has greatly improved, a renewed interest in more complex multi-segment gradient liquid chromatography can be expected in the future, raising the need for better performing gradient design algorithms. We explored the possibilities of a new type of multi-segment gradient optimization algorithm, the so-called "one-segment-per-group-of-components" optimization strategy. In this gradient design strategy, the slope is adjusted after the elution of each individual component of the sample, letting the retention properties of the different analytes auto-guide the course of the gradient profile. Applying this method experimentally to four randomly selected test samples, the separation time could on average be reduced with about 40% compared to the best single linear gradient. Moreover, the newly proposed approach performed equally well or better than the multi-segment optimization mode of a commercial software package. Carrying out an extensive in silico study, the experimentally observed advantage could also be generalized over a statistically significant amount of different 10 and 20 component samples. In addition, the newly proposed gradient optimization approach enables much faster searches than the traditional multi-step gradient design methods.