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Safflower (Carthamus tinctorius L.) is a deep rooted drought tolerant crop that originated in desert environments of the Middle East, and could be very well adapted to the semi-arid Southern High Plains. A field experiment was conducted at Clovis, New Mexico during 2012 and 2013 seasons to assess drought physiology and yield formation of two diverse spring safflower cultivars under different irrigation levels with or without preseason irrigation. One half of the experimental blocks received preseason irrigation of 164 mm in 2012 and 153 mm in 2013 to refill the soil profile utilized by the previous crops, while the other half remained depleted. Five in-season irrigation levels (I-1-I-5) ranging from 88 to 392 mm in 2012 and from 83 to 373 mm in 2013 were imposed on both preseason irrigation and no-preseason irrigation blocks. Higher leaf water potential (psi(I)) was observed under increased water availability either by preseason irrigation or by higher in-season irrigation level in safflower during two observation dates in both years. Osmotic potential at full turgor (psi(pi 100)), photosynthesis rate (P-n) and transpiration rate (T-r) decreased with a reduction in psi(I) under water stress conditions. The relative water content (RWC) was affected only by the in-season irrigation levels in both years. The preseason irrigation increased seed yield of safflower by 39 and 118% over no-preseason irrigation in 2012 and 2013, respectively. A gradual increase in seed yield was observed with an increase in irrigation levels; and the highest irrigation level, I-5 increased seed yield by 85 and 171% over the lowest irrigation level, I-1 in 2012 and 2013, respectively. Seed yield increased with increase in P-n, plant biomass, number of heads per plant, and number of seeds per head but not with 1000-seed weight under increased water availability. Overall, increased availability of water through preseason irrigation or through in-season irrigation levels improved safflower physiology and yield formation. (C) 2015 Elsevier B.V. All rights reserved.