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In the desert southwest of the United States, cayenne pepper (Capsicum annuum L.) is an important crop. It is used in the production of hot sauce mash, the precursor to many hot sauces. Because hand harvest is currently required to accommodate staggered crop development, more uniform maturity is desired to facilitate mechanical harvest to decrease labor costs. This study was performed over 3 years (2009-11) and in two locations in southern New Mexico, resulting in five unique year/location scenarios (environments). Four timings of ethephon (0.56 kg a.i./ha) spray applications were evaluated for their potential to increase red cayenne cv. Mesilla yields and percentage of red pods. If yield increases and pigmentation improvements occur, ethephon may facilitate a once-over mechanical harvest. Ethephon was applied once at four key cayenne growth stages based on heat units accumulated after planting (HUAP): 1400 HUAP (late June to early July), 1800 HUAP (mid-July), 2800 HUAP (late August to early September), and 3100 HUAP (mid- to late September). Application timings corresponded to early bloom, peak bloom, late physiological maturity of plants, and preharvest, respectively. A non-sprayed control was also included. Fresh red, green, and non-marketable pod weights were recorded for each treatment in a once-over simulated machine harvest in October and analyzed for statistical differences. Mid- to late-season (2800-3100 HUAP) ethephon treatments significantly decreased undesirable green pod yield and, therefore, increased red pod percentage in four of five environments. Although a red pod yield increase was only observed in one environment (a drip-irrigated plot in 2010), there were no negative impacts on red pod yield in any environment resulting from ethephon application. In addition, pepper quality (yield of unmarketable pods) was not significantly reduced by ethephon. Previous work has focused on increasing red pod yields with mixed results. The results show that ethephon may synchronize cayenne pepper red fruit maturity necessary for mechanical harvest and reduce the labor involved in removing green pods before processing.