Increasing demands and concerns for reliable supply of liquid transportation fuels make it important to find alternative sources to petroleum-based fuels. One such alternative is cellulosic ethanol. However, several technical barriers have hindered large-scale, cost-effective manufacturing of cellulosic ethanol, such as low density of cellulosic feedstocks (causing high transportation and storage costs) and low efficiency of enzymatic hydrolysis (causing longer processing time and low sugar yield). Ultrasonic vibration-assisted (UV-A) pelleting can increase the density of cellulosic materials and sugar yield in enzymatic hydrolysis. At present, effects of process variables in UV-A pelleting on pellet quality (density, durability, and spring-back) and sugar yield have not been adequately investigated. This paper reports an experimental investigation on UV-A pelleting of wheat straw. A 24 factorial design is employed to evaluate effects of process variables (moisture content, sieve size, pelleting pressure, and ultrasonic power) on output variables (pellet density, durability, spring-back, and sugar yield).