The demand of cotton is increasing but its low production rate cannot fulfill the world requirements. The increase in cotton demand has augmented the production of regenerated cellulosic fibers. Furthermore, cotton has proved to be unsustainable because of the use of huge amount of fresh water, pesticides and insecticides. The purpose of this work is to find out the suitable blend/blends of regenerated fibers so as to replace 100% cotton fabrics. Therefore, mechanical and comfort properties of Tencel fabrics blended with other regenerated cellulose fibers have been compared with 100% cotton to achieve the equivalent or even better end properties. Hence, cotton, viscose, Tencel, modal, and bamboo fibers were taken. Plain woven blended fabrics of 100% cotton and 50:50 blends of Tencel with other regenerated fibers were prepared from normal yarn count of 20 tex. The mechanical properties (warp-wise and weft-wise tensile and tear strengths, pilling, and abrasion resistance) and the comfort properties including air permeability, moisture management properties, and thermal resistance were evaluated. It is found that Tencel blended fabrics show better results than 100% cotton fabrics. Therefore, it is concluded that Tencel blended with these regenerated fabrics can be used to replace 100% cotton fabrics.