Energetic hot spots account for a significant portion of the total binding free energy and correlate with structurally conserved interface residues. Here, we map experimentally determined hot spots and structurally conserved residues to investigate their geometrical organization. Unfilled pockets are pockets that remain unfilled after protein–protein complexation, while complemented pockets are pockets that disappear upon binding, representing tightly fit regions. We find that structurally conserved residues and energetic hot spots are strongly favored to be located in complemented pockets, and are disfavored in unfilled pockets. For the three available protein–protein complexes with complemented pockets where both members of the complex were alanine-scanned, 62% of all hot spots (ΔΔG>2kcal/mol) are within these pockets, and 60% of the residues in the complemented pockets are hot spots. 93% of all red-hot residues (ΔΔG≥4kcal/mol) either protrude into or are located in complemented pockets. The occurrence of hot spots and conserved residues in complemented pockets highlights the role of local tight packing in protein associations, and rationalizes their energetic contribution and conservation. Complemented pockets and their corresponding protruding residues emerge among the most important geometric features in protein–protein interactions. By screening the solvent, this organization shields backbone hydrogen bonds and charge–charge interactions. Complemented pockets often pre-exist binding. For 18 protein–protein complexes with complemented pockets whose unbound structures are available, in 16 the pockets are identified to pre-exist in the unbound structures. The root-mean-squared deviations of the atoms lining the pockets between the bound and unbound states is as small as 0.9Å, suggesting that such pockets constitute features of the populated native state that may be used in docking.