Successful cotton harvest depends on the use of harvest-aid chemicals, but their performance is often inconsistent because of weather conditions. Our objective was to determine weather factors that most influence responses to various harvest aids. A 5-yr study was conducted at 16 locations across the United States. Responses to three defoliants, applied with and without ethephon, were compared with an untreated check. Response data included defoliation, desiccation, boll opening, and regrowth. Weather data collected prior to and following treatment were precipitation and average daily maximum and minimum temperatures. Data taken at time of treatment included cloud cover, air temperature, relative humidity, and wind speed. Correlation and quartile analyses showed that daily minimum temperatures from planting to treatment dominated the weather factors influencing the defoliation response to all harvest aids. High seasonal night temperatures apparently promoted crop maturity and susceptibility to defoliation. Weather had little influence on desiccation. Daily maximum temperatures from planting to treatment, and daily maximum and minimum temperatures after application were the main weather factors influencing the boll opening response to ethephonbased treatments. Although boll opening was promoted by warm weather after treatment, ethephon had a proportionally greater boll opening response under cooler conditions in which boll opening of untreated cotton apparently slowed. Terminal regrowth responses were most evident with relatively moist conditions before treatment and mild temperatures after treatment, which apparently promoted vegetative regrowth in untreated relative to treated cotton. These findings may help improve selection of harvest aids for different weather conditions and climatic regimes.