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In the midsouth USA, soybean is produced either under irrigated or non-irrigated conditions. The objective of this experiment was to show the utility of supplemental irrigation as an alternative to full-season and non-irrigation to achieve high yield and high seed composition. The effects of irrigation and cultivar differences on soybean yield and seed composition were conducted. Two cultivars (Dwight and Freedom) and three irrigation regimes (full-season irrigation, FS; reproductive stage/supplemental irrigation, RI; and non-irrigation, NI) were used. Protein percentage was higher in Dwight under FS and RI than NI. In Freedom, protein percentage was higher under NI than under FS and RI. Under NI, Freedom had higher protein percentage than Dwight, especially in 2004, but lower oil in 2003 and 2004. Cultivars showed significant differences in fatty acids. Yield in Freedom under FS and RI was not significantly different. Nitrogen fixation was substantially higher under NI conditions. The results indicate that irrigation management and cultivar selection significantly affect seed composition and yield. Protein increase in Freedom under non-irrigated conditions may benefit producers for high protein seed under dry-land conditions. Supplemental irrigation at the reproductive stage may be a possible alternative for full season irrigation for the cultivar Freedom.