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The performance of seed cotton cleaning equipment in commercial gins is not well documented. Most research reporting cleaning efficiencies of this machinery was performed in the laboratory under optimal conditions, while commercial gins must often process cotton with high moisture or foreign matter content. Seed cotton samples were collected from Mid-South gins in 2009, 2010, and 2011. Seed cotton cleaning efficiency was 62.1% in 2010, significantly higher than in 2009 (44.3%) or 2011 (46.9%). Modules in 2010 contained seed cotton with fewer motes, more leaf, and lower moisture content, likely resulting in higher cleaning efficiency. Seed cotton cleaning efficiency varied widely between gins, even during the same year. Regression analysis indicated that the content of the seed cotton in the module had a larger effect on the content of the seed cotton after cleaning than the equipment used by the gin. However, additional cylinder cleaners reduced leaf content and additional extractors reduced hull content. More research is needed to recommend using additional or fewer seed cotton cleaners in particular situations.