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This study was undertaken in the South Eastern Anatolia region of Turkey during the 2006 and 2007 growing seasons to investigate the seed set efficiencies (SSE) of ten cotton cultivars grown in semi-arid climatic conditions. SSE changed by year by approximately 1-2%, averaging 87-88% in both of the study years, respectively. Mean values for varieties ranged from 86.5% (SG-125) to 89.9% (DPL-5111) in 2006 and from 86.2% (SG-125) to 89.5% (Fantom) in 2007. There were significant differences (p<0.05) among the cultivars according to harvesting time, except for the first harvest in 2006. Although differences were small, generally, it was observed that SSE diminished in flowers opened at the end of the growing season. The results showed that SSE was significantly affected (p<0.05) by cultivars, harvesting times and years. Additionally, SSE was significantly (p<0.05) and positively (r=0.39* and r=0.44*) correlated to seed cotton yield and seed yield in 2007. There was a significant difference in the number of seeds within the bolls formed early or late in the season, indicating bolls harvested at different times throughout the growing season could not be used for seed production. However, study results strongly indicated that seeds from the first harvest should be used for cotton seed production.