The effects of inclination angle and plate spacing on the separation of heavy water from water isotope mixture in continuous-type flat-plate thermal diffusion columns, has been investigated with the consideration of a fixed operating expense. Although there do not exist simultaneously the optimal angle of inclination and optimal plate spacing for maximum separation, increasing either the inclination angle or plate spacing will increase, respectively, the optimal plate spacing or optimal inclination angle, as well as the corresponding maximum separations. The equations for the optimal inclination angle and optimal plate spacing, as well as the corresponding maximum separations, have been derived. Considerable improvement in separation is achievable if the operations are conducted with the optimal operating conditions.