The temperature regiocontrol of intramolecular cyclization of di-hydroxysecoacids was investigated. A simple and efficient regiocontrol of the macrolactonization reaction was obtained by controlling the reaction temperature. There are two physico-chemical factors which contribute to the entropic term: the higher number of conformers of the larger ring and vibrational contributions arising from low frequency modes. It was found that the energetic factors favor the formation of smaller ring, while the entropic factors drive the cyclization towards the formation of larger ring.