The effect of the column number on deuterium recovery from H–D gas mixture in the countercurrent-flow Frazier scheme of thermal diffusion columns with the total sum of column heights fixed, has been investigated. The equations for predicting the optimal number of columns and the corresponding maximum separation have been derived. Considerable improvement in deuterium recovery is obtainable if the multi-column device with the optimal number of columns is employed, instead of using the single-column device with the same total sum of column heights, especially for the cases of higher volume flow-rate operation and larger total sum of column heights. Furthermore, countercurrent-flow operation is much better than forward-flow operation.