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Water shortage is a key constraint to sustainable agricultural production in Xinjiang, Northwest China. To enhance the use efficiency of valuable irrigation water resources, a 2-year experiment (2010-2011) was conducted to quantify the response of cotton (Gossypium hirsutum L.) growth and yield to different degrees of deficit irrigation (DI) regimes; to determine the effects of DI on the characteristics of water use for cotton, seasonal water use, available soil water in the root zone, soil water depletion, evapotranspiration (ET)-based water use efficiency and irrigation-based water use efficiency, and to determine the best DI regime for optimal water-saving and yield output. The plots were irrigated at 100% (100ET), 85% (85ET), 70% (70ET), 55% (55ET) and 45% (45ET) of the regional ET of cotton in northern Xinjiang. The effect of DI irrigation on water use characteristics was evaluated by analyzing available soil water and soil water depletion in the root zone along with water use efficiencies of cotton. The study showed that the growth, water use characteristics and yield of cotton varied with irrigation regime. Seasonal ET and seed cotton yield were linearly correlated with irrigation amount. The second-order polynomial equation best approximated water-yield relationship of cotton in the study area. Cotton yield response factor was 0.65, suggesting limited water conditions were suitable for cotton cultivation. Economic evaluation of DI treatments confirmed that the yield loss was less than 10% under 70ET and 85ET, which was acceptable for greater sustainability. The results suggested that proper DI schemes were necessary for sustainable cotton production in the region. While irrigation at 85ET was safe for high cotton yield, irrigation at 70ET was a viable alternative under limited irrigation water availability.