The gem-disubstituent effect in intramolecular alkyne-azide 1,3 dipolar cycloaddition (AAC) reaction is demonstrated with O-propargylated azido compounds 2a−d. The experimental kinetic data and thermodynamic parameters obtained from computational studies, were correlated with the 'gem-disubstituent effect'. In disubstituted compounds 2b and 2c, the decrease in internal angle (θ) increases the rate of AAC by 9.0 and 8.0 fold, respectively, as compared to reaction of unsubstituted 2a. This increase in rate was attributed to the decrease in Gibbs free energy of activation (ΔG#) for AAC reactions of 2a−c. While remarkable rate acceleration in AAC reaction of sugar derivative 2d (18.0 times more than 2a) was due to the collective effect of decrease in internal angle θ and 'reactive rotamer effect'. The steric assistance exerted by two O-isopropylidene groups in 2d compresses azide and alkyne groups so as to attain stereopopulation controlled increase in stability of 'syn-rotamer' by 0.59 kcal/mol as compared to its 'anti-rotamer'. This resulted in lowering of ΔG# for reaction of 2d (18.09 kcal/mol) against AAC of 2a (20.42 kcal/mol) which is responsible for the unusual rate enhancement in 2d by 18.0 fold to the extent that the reaction occurs at ambient temperature within 18 h, in high yield.