The limited window of opportunity for glyphosate postemergence (POST) over-the-top applications in glyphosate-resistant cotton poses a problem for growers where a midseason salvage weed control remedy is necessary. The objectives of these experiments were to compare glyphosate and MSMA for midseason weed control and their subsequent effect on cotton fruiting characteristics and yield. Glyphosate at 0.85 kg ai/ha was more effective than MSMA at 1.7 kg ai/ha for POST control of sicklepod, redweed, and pitted morningglory. Single glyphosate treatments applied at the 8-, 10-, or 12-leaf cotton stage resulted in less-effective weed control than when applied at the four-leaf cotton stage. Glyphosate applied at the four-leaf cotton stage followed by a sequential POST-directed application at 6-, 8-, 10-, or 12-leaf cotton stage increased season-long weed control and yield compared with a single application at the four-leaf stage. Both glyphosate and MSMA controlled Florida beggarweed, regardless of POST application timing. Generally, cotton was more tolerant to glyphosate than MSMA when applied over-the-top. Glyphosate applied POST over-the-top to weed-free 12-leaf cotton resulted in a 19 and 14% yield loss compared with the weed-free nontreated cotton in 1997 and 1999. MSMA reduced yield by 58 and 36% in 1997 and 1999, respectively. Glyphosate did not affect weed-free cotton fruit development or yield when applied over-the-top to four-leaf cotton or when a POST-directed application was followed at the 12-leaf stage.