Polyurethane (PU) foams are classified as physically nonrecyclable thermosets. The current effort of sustainable and eco-friendly production makes it essential to explore methods of better waste management, for instance by modifying the structure of these frequently used polymers to enhance their microbial degradability. The presence of ester links is known to be a crucial prerequisite for the biodegradability of PU foams. However, the impact of other hydrolysable groups (urethane, urea and amide) occurred in PU materials, as well as the supramolecular structure of the PU network and the cellular morphology of PU foams, is still relatively unexplored.In this work, fully aliphatic PU foams with and without hydrolyzable amide linkages were prepared and their aerobic biodegradation was investigated using a six-month soil burial test. Besides the variable chemical composition of the PU foams, the influence of their different supramolecular arrangement and cellular morphologies on the extent of biodegradation was also evaluated. Throughout the soil burial test, the release of carbon dioxide, and enzyme activities of proteases, esterases, and ureases were measured. At the same time, phospho-lipid fatty acids (PLFA) analysis was conducted together with an assessment of microbial community composition achieved by analysing the genetic information from the 16S rRNA gene and ITS2 region sequencing.The results revealed a mineralization rate of 30–50 % for the PU foams, indicating a significant level of degradation as well as indicating that PU foams can be utilized by soil microorganisms as a source of both energy and nutrients. Importantly, microbial biomass remained unaffected, suggesting that there was no toxicity associated with the degradation products of the PU foams. It was further confirmed that ester linkages in PU foam structure were easily enzymatically cleavable, while amide linkages were not prone to degradation by soil microorganisms. In addition, it was shown that the presence of amide linkages in PU foam leads to a change in the supramolecular network arrangement due to increased content of hard segments, which in turn reduces the biodegradability of PU foam. These findings show that it is important to consider both chemical composition and supramolecular/macroscopic structure when designing new PU materials in an effort to develop environmentally friendly alternatives.