Safflower seeds have a high content of oil of good nutritional value. In cereal-based rotations, it can help diversify cropping systems, break disease cycles and control grass weeds. Three winter safflower cultivars (Goldasht, Padideh and K.w.2) were evaluated during two years under five different water regimes in Karaj, Iran. The five water regimes consisted of a control (full irrigated) treatment and four treatments where irrigation was interrupted at bud formation, beginning of flowering, end of flowering, and seed filling. Measurements involved yield and yield components, biomass, plant height, seed oil content, phenological traits and agronomic and irrigation water use efficiency (WUEa and WUEi , respectively). No year effect was noted for most measured traits. Highly significant effects of the water regime were found on seed yield, oil yield, days to maturity and the number of capitula per plant. Seed yield and the number of capitula per plant were particularly affected by water shortage at bud formation (36.5 and 37.8%, respectively). The lowest agronomic WUEa was consequently when irrigation was stopped at beginning of flowering (28.9% less than in full irrigated) and at bud formation (18.3% less than in full irrigated). WUEi decreased with the quantity of water supplied by irrigation. Water regime did not affect seed oil content. Significant effects of cultivar were found for seed yield, number of capitula per plant, 1000-seed weight, plant height, seed oil content and phenological traits, except days to flowering. Padideh yielded 12.8% more than K.w.2 and 7.6% more than Goldasht. Seed yield was significantly associated with the number of capitula per plant but not with the number of seeds per capitulum and 1000-seed weight. These results demonstrate that bud formation is particularly sensitive to water deficit, and will allow better water management of safflower in semi-arid agriculture.