Reactivity Controlled Compression Ignition (RCCI) is one of the most promising solutions among the low temperature combustion concepts, in terms of thermal efficiency and pollutant emissions. However, for values of brake mean effective pressure higher than 10 bar, in-cylinder peak pressure rise rates tend to be too high, limiting the specific power of any 4-Stroke (4S) engine. Such a limitation can be canceled by moving to the 2-Stroke (2S) cycle. Among many alternatives, the “Uniflow” scavenging system with exhaust poppet valves on the cylinder head allows the designer to reproduce the same identical combustion patterns of a 4-stroke RCCI engine, while increasing the indicated power output. The goal of the paper is to explore the potential of a 2-stroke RCCI engine, on the basis of a comprehensive experimental campaign carried out on a modified automotive 2.0 L, 4-stroke, four-cylinder, four-valve diesel engine. The developed prototype can run with one cylinder operating in 4-stroke RCCI mode (gasoline–diesel), while the others work in the standard diesel mode. A One Dimensional-Computational Fluid Dynamics (1D-CFD) model has been built to predict the performance of the same prototype, when operating all four cylinders in RCCI mode. In parallel, an equivalent 2-stroke RCCI virtual engine has been developed, by means of 1D-CFD simulations and empirical assumptions. A numerical comparison between the 4S and the 2S engines is finally presented, in terms of performance and emissions at full load. The study demonstrates that a 2S RCCI engine can maintain all of the advantages of the RCCI combustion, strongly reducing the penalization in terms of performance, in comparison to a standard 4S diesel engine.