Safflower has been transformed for field scale molecular farming of high-value proteins including several pharmaceuticals. Viable safflower seed remaining in the soil seed bank after harvest could facilitate seed and pollen-mediated gene flow. Seeds may germinate in subsequent years and volunteer plants may flower and potentially outcross with commodity safflower and/or produce seed. Seeds from volunteers could become admixed with conventional crops at harvest, and/or replenish the seed bank. Seed in following crops could be transported locally and internationally and facilitate gene flow in locations where regulatory thresholds and public acceptance differ from Canada. Seed-mediated gene flow was examined in three studies. Safflower seed loss and viability following harvest of commercial fields of a non-transgenic cultivar were determined. We assessed seed longevity of transgenic and non-transgenic safflower, on the soil surface and buried at two depths. Finally, we surveyed commercial safflower fields at different sites and measured density and growth stage of safflower volunteers, in other crops the following year and documented volunteer survival and viable seed production. Total seed loss at harvest in commercial fields, ranged from 231 to 1,069 seeds m⁻² and the number of viable seeds ranged from 81 to 518 seeds m⁻². Safflower has a relatively short longevity in the seed bank and no viable seeds were found after 2 years. Based on the seed burial studies it is predicted that winter conditions would reduce safflower seed viability on the soil surface by >50%, leaving between 40 and 260 viable seeds m⁻². The density of safflower volunteers emerging in the early spring of the following year ranged from 3 to 11 seedlings m⁻². Safflower volunteers did not survive in fields under chemical fallow, but in some cereal fields small numbers of volunteers did survive and generate viable seed. Results will be used to make recommendations for best management practices to reduce seed-mediated gene flow from commercial production of plant molecular farming with safflower.