A single‐center, open‐label, and dose‐escalation clinical trial has been performed using a novel electrochemical transdermal patch comprising a drug‐loaded hydrogel sandwiched between two silver electrodes. The lower electrode is attached flatly to skin via an adhesive layer. This noniontophoretic device produces flux enhancement via voltage‐induced electrolysis of the water in the hydrogel. A voltage application of 2 V over 60 s produced release of approximately 315 to 340 μg of fentanyl from a patch. A single‐voltage application at t = 16 h produced a maximum plasma level of approximately 200 pg/mL before patch removal at t = 41 h. Consecutive voltage applications at t = 16 h and t = 40 h produced a maximum plasma level of approximately 730 pg/mL. The lag time between voltage application and achievement of a plasma profile plateau is longer than that reported for an iontophoretic patch. The patch's advantage is production of an on‐demand plasma profile without the use of potentially irritating iontophoresis. In contrast to a passive transdermal system, it is possible to adjust the plasma profile by using voltage application. It is not necessary to apply a continual current, in contrast to iontophoretic systems. © 2012 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 101:2262–2268, 2012