Tertiary amine catalysts are essential components in manufacturing polyurethane materials. The low-emission requirements for indoor applications are typically achieved by employing tertiary amines with catalytically active N,N-dimethyl groups as the base catalyst and a longer alkyl substituent with a reactive end, that is, alcohol or amine, to incorporate it in the polyurethane matrix. N,N-dimethyl groups are, however, oxidized when exposed to air and lead to undesired formaldehyde emissions. Here, we employ modern quantum chemical methods to understand design principles how the structure of tertiary amine catalysts having N,N-dimethyl groups can be modified to avoid this source of formaldehyde formation but still preserve their catalytic activity. We found the pyrrolidine derivative of commonly used N,N-dimethylated catalysts to be the most promising candidate and developed design principles to rationalize why longer alkyl chains or larger ring sizes inhibit the catalytic activity. The computationally predicted catalyst performances were confirmed experimentally in model polyurethane systems for selected amine catalysts, and emission measurements showed that the formaldehyde emission was completely suppressed when pyrrolidine derivative was used as a catalyst. Our results further illustrate how condensed phase reactions can be predicted using quantum chemical methods and that to account for steric hindrance near the reaction center, it was also necessary to include conformational energy contributions in the calculated activation free energies.