A conformational analytical study of a series of trimethylsilyloxy- (TMSO) and tert-butoxy- (TBO) substituted 1,4-dioxanes was performed using NMR techniques. It was found that the TMSO and TBO groups (in contrast to MeO, AcO, and PhO substituents2) alleviate the anomeric effect. Arguments based on molecular mechanics (MM2-parametrized for the anomeric effect) and MO ab initio calculations of ROCOR/ (R = CH3, H; R' = SiH3) at various levels help rationalize this behavior, by isolating and identifying steric and electronic contributions. The electronic factors are (i) strong attractive nonbonded OSi…-0 interactions within the R-O-C-O-Si system, which reduce considerably the O-C-O-Si dihedral angle (down to 0°) and the energy of the “ag” (equatorial) form vs. the “g+g+” one and (ii) inductive electron donation by SiMe3(or CMe3) which lowers the electronegativity of TMSO (or TBO). Steric factors and (p →d)π bonding are negligible. A single-crystal X-ray analysis of 2,5-di-tert-butoxy-l,4-dioxane revealed structural data in line with all the above.