The biobased polyester poly(ethylene 2,4-furanoate) (2,4-PEF) is a potentially interesting yet insufficiently studied polymer whose resistance to crystallization fundamentally stems from the asymmetric nature of the 2,4-furandicarboxylic acid monomer. A combination of vibrational spectroscopy (infrared, Raman and inelastic neutron scattering) and ab initio calculations has been used to assess the conformational and regiochemistry preferences of 2,4-PEF. The latter polymerizes following a random distribution of monomer orientation, thereby rendering the formation of periodic interchain C-H center dot center dot center dot O contacts wholly unfeasible and ultimately favoring the formation of randomly coiled chains based on gauche-ethylene glycol segments. In the absence of C-H center dot center dot center dot O stabilization, the ordered crystalline arrangement is disfavored and polymer chains-adopting several quasi isoenergetic structures-prefer to solidify into an amorphous mess.