Glyphosate-resistant (GR) alfalfa offers growers new options for weed control in alfalfa. One potential benefit of using GR alfalfa is increased longevity of an alfalfa stand under frequent harvests. It was hypothesized that GR alfalfa would have a greater longevity because of removal of weed interference with minimal crop injury. To study GR alfalfa yield, weed invasion, alfalfa stand persistence, and relative forage quality (RFQ), a field experiment with three weed control methods (no herbicide, glyphosate, and hexazinone) under two harvest frequencies (high and moderate) was established in August 2003 at the Michigan State University Agronomy Farm in East Lansing, MI. Forage yield of established alfalfa was not adversely affected by herbicide treatments. There were no differences in weed biomass between alfalfa treated with glyphosate and that treated with hexazinone, except in 2007. Average GR alfalfa stand density decreased approximately 90% (from 236 to 27 plant m−2), and yield decreased approximately 30% (from 11.04 to 7.87 Mg ha−1) during the 7-yr period (2004 to 2010) of the experiment. Stand density of GR alfalfa showed natural thinning during the 7-yr period regardless of harvest intensity or herbicide treatment. In most production years (4 out of 5 yr), relative forage quality of GR alfalfa was higher under a high-intensity harvesting system (4 to 5 harvests yr−1) than it was with a moderate intensity harvesting system (3 to 4 harvests yr−1). Relative forage quality was not affected by weed removal with herbicides in most years. Weed removal and harvest intensity in established GR alfalfa had no effect on stand persistence.