Under certain conditions, application of glyphosate to glyphosate-resistant (GR) cotton can lead to fruit shedding and yield reductions. Field studies were conducted at the Texas Agricultural Experiment Station using GR cotton, cv. ‘DeltaPine 5690RR’, to determine if application method and timing affect cotton fruit retention. Glyphosate at 1.12 kg ai ha−1was precisely postdirected (PD), postdirected with 25% foliage coverage (PDFC), or applied over the top (OT) at the 8- or 18-leaf stage after an initial topical application of 1.12 kg ha−1glyphosate at the four-leaf stage. In one of the years of this study, 8 PD, 18 PDFC, and 18 OT reduced yield. In 1999 and 2000, 8 PDFC and 8 OT applications of glyphosate caused yield loss, mainly due to lower mean boll weight. Glyphosate applied topically at the eight-leaf stage also affected the Position 1 boll retention throughout the plant in both years. Glyphosate contact with leaves and stems should be avoided when applying glyphosate after the four-leaf stage to prevent possible yield loss.