This study focuses on least-cost farm-to-mill cotton cleaning configurations employing survey, regression, and simulation techniques. The resulting least-cost cotton cleaning configurations, employing standard textile technology, included the use of one lint cleaning in the ginning stage. The use of a field cleaner in the harvesting stage was also found to be optimal with some variation based on the desired yarn quality. Results of the study indicated that the optimal cleaning configurations were distinctly different from currently used practices, such that appropriate changes could save the cotton industry between $0.30 and $0.60 per bale of cotton, depending on the desired yarn quality.