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The present work compared the agronomic traits, chemical composition, fatty acid profile, and in vitro fermentation characteristics of twelve accessions of Amaranthus spp., belonging to A. cruentus, A. hybridus, A. hypochondriacus, and A. tricolor, grown in a semiarid Mediterranean area. Among accessions, Benin and Arizona (A. cruentus) and Pennsylvania (A. hypochondriacus) showed the highest seed yield (on average, 322.1 g m−2), while Taiwan (A. tricolor) and India and Iowa (A. hypochondriacus) the highest thousand seed weight (on average, 0.81 g). Among the species, A. hypochondriacus showed the highest crude protein (16 g 100g−1), starch (51.5 g 100g−1), and soluble detergent fiber (2.03 g 100g−1) contents and the most favorable in vitro fermentation characteristics with the highest short-chain fatty acid (SCFA 52.6 mmol g−1) and butyric acid (20.7% SCFA) production together with the lowest crude fiber (4.93 g 100g−1) and insoluble dietary fiber (12.5 g 100g−1) content. Arizona (A. cruentus) showed the highest level of monounsaturated fatty acids (32.67 g 100g−1), Ohio (A. hybridus) had the highest levels of polyunsaturated fatty acids (44.62 g 100g−1) and n6-PUFA (44.21 g 100g−1), and India (A. hypochondriacus) had the highest level of n3-PUFA (0.63 g 100g−1). A. hypochondriacus exhibited not only desirable nutritive characteristics, agronomic traits, and suitability to Mediterranean growing conditions, but also a potential beneficial effect. Nonetheless, it is recommended to run longer-term field trials to confirm these findings and to assess the genotype by environment interaction either with current accessions or others from the wide Amaranth germplasm available. [ABSTRACT FROM AUTHOR]