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Effect of graded levels of major nutrients and biofertilizers on yield, nutrient content and nutrient uptake of safflower growing in vertisols was investigated in field experiment carried out on clayey soil at College of Agriculture, Nagpur during rabi season using variety AKS/S-41 in 2011-12. The experiment was conducted in a Randomized Block Design (RBD) with three (3) replications and nine (9) treatments. N and P fertilizers each at 40 kg ha-1 were applied. The sources of N and P were urea and single super phosphate. The results of the study showed that yield, nutrient content and uptake N, P, K, parameters of safflower were significantly found highest in the treatment of RDF alone or in combination with Azospirillum + PSB. The seed and straw yield of safflower was also significantly highest in the same treatments. It is concluded that combination of biofertilizer and major fertilizers significantly improved the yield, nutrient content and uptake of safflower.