A liquid chromatography system and method utilizes a mobile phase comprising liquified compressible gas and miscible organic solvents. The compressible fluid may be carbon dioxide (CO2). Liquid CO2 tapped from an existing source is depressurized through a flow control metering station before adding solvent. The mobile phase flows through a sample vessel containing analytes and chromatography column for sample separation. A back pressure regulator maintains a set elution pressure in the chromatography column. CO2 advantageously remains in liquid phase for elution in the column, thereby avoiding two-phase conditions adversely affecting analyte resolution. An equilibration bypass flow loop may be provided to separate normal sample elution from initial CO2 flow equilibration, thereby allowing rapid exchange of samples with minimal downtime. System CO2 pressures less than 100 bar and room temperature may be used during the process, thereby obviating the need for high pressure pumps and chillers of supercritical fl
