Spot colors have a wide range of applications in commercial as well as packaging printing. Accuracy in spot color matching and its consistency depend on the premedia software. Digital printers used for the proofing are also crucial to the quality control process. Due to the advancements and development in digital printers, inks, proofing substrates, and systems, the spot color proofing can be much cheaper compared to the conventional method. Currently, premedia software does not have ways to deal with spot color overprints, and therefore, there is no way to predict final spot color in the case print order changes. This research was aimed to study the reproduction of the spot colors with the help of premedia software such as SmartColourTM iVue, Adobe Photoshop, and a raster image processor (RIP) through inkjet printers for flexo packaging. A test chart was created with three different types of spot color inks-red, green, orange-through ProfileMaker 5.0.8. This test chart was printed on a Comco Commander flexographic press with different print sequences on C1S and SBS board. The CIE L*a*b* values of printed test charts were measured using MeasureTool software with an X-Rite i1-iO scanning spectrophotometer. The spot colors were proofed on a semi-matte substrate printed on two different Epson Stylus Pro printers. This substrate was printed, using different prepress and color management software: SmartColourTM iVue, Photoshop, and full RIP. Finally the CIE L*a*b* values for the press and digital printed test chart were compared and for different print sequences ?E values were calculated, considering the press sheet as a standard, which showed that the proofing of the spot color and its reproduction through SmartColourTM iVue was better compared to RIP software and Adobe Photoshop.