Although transcranial Direct Current stimulation (tDCS) shows promise in the treatment of major depressive episodes, the optimal parameters and population to target remain unclear. We investigated the clinical interest of a 10 session tDCS regimen in patients with mild to severe treatment-resistant depression, in a pilot double-blind, randomized sham-controlled trial. tDCS was delivered over 5 consecutive days (two 30 min sessions per day separated by at least 2 h, 2 mA). The anode and cathode were placed over the left and the right dorsolateral prefrontal cortex, respectively. One month after tDCS, we observed significantly fewer patients who achieved remission (MADRS₁₀ < 10) in the sham group (0 out of 18 patients) than in the active group (5 out of 21 patients; p = 0.05). However, no significant difference was observed between the groups regarding the mean scores of severity changes throughout the study period. Bifrontal add-on tDCS delivered twice per day over 5 days, in combination with antidepressant medication, can be a safe and suitable approach to achieve remission in patients with mild to severe treatment-resistant major depressive disorder. However, in regards to the pilot nature and limitations of the present study, further studies are needed before any frank conclusions can be made regarding the use of tDCS with the proposed parameters in clinical settings.