The architecture of hydrophobically modified polymers can be tailored to produce variants with different levels of functionality. This allows industry to apply rational design methods for the development of more environmentally friendly materials. In the present work, the ecotoxicity of six variants of hydrophobically modified poly(acrylic) acids (HMPAA), obtained by changing the crosslinked conformation, insertion position, and length of the hydrophobic groups, was assessed for the (i) bioluminescence production of Aliivibrio fischeri; (ii) population growth rate of Raphidocelis subcapitata and Chlorella vulgaris; (iii) mortality of Brachionus calyciflorus; (iv) feeding inhibition, somatic growth rate, reproduction, and mortality of Daphnia magna; and (iv) mortality and somatic growth rate of Pelophylax perezi tadpoles. The concentrations causing 50% and 20% of effects (L(E)C50 and 20, respectively) ranged from 9.64 up to > 2000mg·L-1 for all six HMPAA and species. The bacterium A. fischeri and tadpoles of P. perezi were the most sensitive and most tolerant organisms to the six tested HMPAA, respectively. The computed 5% hazard concentrations (computed on the basis of L(E)C50s) showed that HMPAA1 (13.0mg·L-1) and HMPAA2 (26.1mg·L-1) were the most toxic variants, while HMPAA6 (233mg·L-1) the least one. These results suggest HMPAA6 (with low crosslink percentage modified by the addition of long and short hydrophobic groups at the surface) to be the most environmentally friendly variant and should be preferentially considered to be used in consumer products, compared to the other five studied variants.