Abstract NMR spin–lattice relaxation times (T1) for nucleus D of D2O in deuterated formamide (FA-d3)–D2O mixtures were measured up to 80 mol % of FA-d3 at 25 °C under pressure up to 196.1 MPa. To discuss the pressure effect on the dynamic behavior of water molecules in the mixtures, the reorientational correlation times (τc) of D2O molecules were estimated from the quadrupole coupling equation. τc monotonously increased with increasing FA-d3 content at all pressures studied. However, τc apparently decreased with increasing pressure until 20 mol % of FA-d3, while over 40 mol % of FA-d3 the pressure coefficient of τc (∂τc/∂P) became positive and larger with increasing FA-d3 content. A negative pressure coefficient would indicate the existence of three-dimensional hydrogen-bonded network structure of water, and a positive one would be ascribed to the strengthening of dipole interactions and hydrogen bonds between FA-d3 and D2O by compression. In order to investigate the pressure effect on the reorientational dynamics of water molecules in detail, we performed molecular dynamics (MD) simulations paying attention to the pressure effect on hydrogen-bonding and dipole interactions.