Twin-screw boosting technology has shown a versatile and reliable performance for a wide range of gas fractions at inlet streams. However, the use of positive displacement rotating pumps in field conditions is restricted to constant displacement pumps (i.e., no reduction of fluids volume), due to the variability of the gas fraction in the produced streams, which can eventually be zero. On the other side, when operating with high inlet gas volume fractions and high compression ratios, the constant displacement condition leads to a very inefficient operation, mainly due to internal liquid recirculation and uneven distribution of the power delivered to the fluids stream along the screw, producing higher wear, uneven dilatation and eventual rotor/stator interference. Beyond the energy efficiency issues, this condition can significantly shorten the pump lifespan, making their application unfeasible in deep-water environments due to the high cost of maintenance. In this paper, an alternative for dealing with high differential pressures and highly variable gas volume fractions is studied. This consists in dividing the compression process into two or more pumps, which displacements are controlled through the rotation speed, according to the gas fraction at inlet of the pumping system. A theoretical analysis and an experimental investigation of the performance of a boosting system based on the serial arrangement of twin-screw pumps is presented. Results show that the system performance is significantly increased in terms of volumetric and energetic efficiencies when operating in serial arrangement. Some recommendations for the system design are presented based on the experience gained during the investigation.