Alfalfa (Medicago sativa L.) cultivars developed for improved digestibility by conventional breeding or genetic modification have not been evaluated in eastern Canada. This study compared yield, nutritive value, and profitability of two reduced-lignin genetically modified (GM) cultivars, three conventionally selected for low lignin or high pectin, and one population with improved stem degradability, with two commercially adapted cultivars as controls. Alfalfa was harvested at the early bud (intensive management) or early flower (extensive management) stage of development during the first post-seeding year at three sites and the second post-seeding year at one site. All cultivars/populations had similar annual dry matter (DM) yields, except for the lower DM yield (−20%) of the improved stem degradability population. Conventionally selected cultivars for improved digestibility did not differ from control cultivars for in vitro DM digestibility (IVTD) and neutral detergent fiber digestibility (NDFd). Reduced-lignin GM cultivars, however, had a greater IVTD and NDFd (+10%) and less lignin (−10%) than control cultivars at the same stage of development. Reduced-lignin GM cultivars under extensive management had similar NDFd and greater annual DM yield (+1 to 2 Mg DM ha⁻¹), but reduced total digestible nutrients (−41 to 44 g kg⁻¹ DM), in comparison to control cultivars under intensive management. Using partial budget analysis, the comparison of more digestible GM cultivars to the control cultivars resulted in an increase in annual farm net profits ranging from CAD$7.40 to $79.60 cow⁻¹ year⁻¹ depending on stage of development at harvest. Further investigations are needed to quantify the performance of dairy cows fed cultivars with improved digestibility.