It is well known that dye sublimation inks are designed to bond with polymers. In the textile industry, however, the most common printed textiles are made of cotton and cotton blends. 100% cotton accounts for approximately 45% of the textile market. Recent developments in heat transfer paper carrier made it possible to use heat transfer printing on 100% cotton fabrics. Color reproduction capability of a heat thermal print is highly related to the amount of dye transferred. To achieve high dye transfer efficiency and obtain the best color reproduction capability, three primary parameters, heat transfer temperature, dwell time in the heat zone, and pressure, need to be taken into account. The main purposes of this experimental study are: first, to identify the most important factors that influence color reproduction on 100% cotton fabrics using heat transfer printing; second, to establish optimum process operating conditions so that the maximum yield of color gamut and optical density could be obtained. The experiment was conducted using a randomized 2³ factorial design in which every factor was run at two specified levels (1 = high level, −1 = low level). The factorial levels were determined based upon the practical operating conditions of the heat transfer press. Three independent factors in this study are: dwell time in the heat zone (X₁), transfer temperature (X₂), and pressure (X₃). Color reproduction capability was evaluated in terms of optical density and gamut volume. It was found that pressure (X₃) is the dominant factor affecting color reproduction on 100% cotton fabrics.