The relation between vacancies and vacancy clusters evolution and the H(2) desorption kinetics was studied in nanocrystalline Mg samples submitted to successive H(2) sorption cycles. Vacancy defects were detected by positron annihilation lifetime spectroscopy while the desorption process was monitored measuring the H(2) desorption flux. During H(2) sorption cycles, vacancies disappear, the number of vacancy clusters increases, and the crystalline quality of the Mg grains increases. The disappearance of intragranular vacancies is followed by an acceleration of the H(2) desorption process. This is attributed to the increase of vacancy clusters at grain boundaries which assist the Mg nucleation in the hydride to metal phase transition. For H(2) sorption cycles, the values of vacancy and vacancy cluster concentrations were obtained into the frame of the positron diffusion trapping model and the size of the involved vacancy clusters was evaluated by ab initio calculations of positron annihilation rates in Mg.