The energetics of intramolecular recognition processes are governed by the balance of pre‐organization and flexibility, which is often difficult to measure and hard to predict. Using classical MD simulations, we predict and quantify the effective strength of intramolecular hydrogen bonds between donor and acceptor sites separated by a variable alkyl linker in several solvents and crowded solutions. The balance of entropic and enthalpic contributions poses a solvent‐dependent limit to the occurrence of intramolecular H‐bonding. Still, free energies show a constant offset among different solvents with, for example, a 13 kJ mol−1 difference between water and chloroform. Molecular crowding shows little effect on the thermodynamic equilibrium, but induces variations on the H‐bond kinetics. The results are in quantitative agreement with experiments in chloroform and showcase a general strategy to investigate molecular interactions in different environments, extending the limits of current experiments towards the prospective prediction of H‐bond interactions in a variety of contexts.