A multi-dimensional liquid chromatography system includes first and second liquid chromatography systems. The first system is configured for providing a first chromatographic separation of a sample fluid comprised in a first mobile phase and to provide a first effluent including at least a portion of the separated sample fluid. The second system is configured for providing a second chromatographic separation of at least a portion of the first effluent comprised in a second mobile phase. A control unit is configured to operate the first liquid chromatography system by maintaining a first flow rate of the first mobile phase substantially constant during the first chromatographic separation, and to operate the second liquid chromatography system during the second chromatographic separation according to a control value different from the second flow rate, so that a variation in the control value can lead to a variation in the second flow rate.