Targeted grazing uses livestock to address woody plant encroachment, flammable biomass accumulations, exotic weed invasions, and other management issues. In principle, a feature distinguishing targeted grazing from production-orientated grazing is stocking regimes (i.e., rates, timings, and durations) are chosen to encourage heavy defoliation of unwanted plants at sensitive growth stages. In practice, there are limited data available to guide stocking regime choices. Those data that do exist derive mostly from short-term studies, so the long-term effects of targeted grazing most concerning to managers remain highly uncertain. In a previous study, we imposed clipping treatments to identify defoliation levels and timings effective against the invader leafy spurge (Euphorbia esula L.). Most treatments simulated defoliation by sheep, the animal most commonly used for leafy spurge grazing, though a baseline treatment simulated defoliation by cattle, an animal tending to avoid leafy spurge. The two most effective treatments, which gave similar responses through the end of the previous study, defoliated leafy spurge and other species either before or during leafy spurge flowering. One goal of the current study was to determine if these responses remained similar or diverged over 5 additional treatment years. The other goal was to determine if differences between simulated sheep and cattle grazing treatments increased over time. In the current study, it became increasingly clear that defoliation before flowering was most damaging to leafy spurge, even though defoliation during flowering removed greater leafy spurge biomass. Compared with simulated cattle grazing, simulated sheep grazing before flowering reduced leafy spurge biomass production 74% (52%, 86%) [mean (95% confidence interval)] and increased resident species (mostly grasses) biomass production 40% (14%, 74%) by study's end. Leafy spurge biomass differences between treatments increased gradually over the study period, suggesting long-term research is needed to accurately compare targeted grazing treatments.