Background/aims: Among the causes related to the development or perpetuation and aggravation of dry eye disease, oxidative reactions may have a role in the pathogenesis of this disorder. Antioxidants, such as iodide, have shown a strong effect in preventing the oxidative damage to constituents of the anterior part of the eye. In this clinical trial the effectiveness of iodide iontophoresis and iodide application without current in moderate to severe dry eye patients was compared. Methods: 16 patients were treated with iodide iontophoresis and 12 patients with iodide application without current for 10 days. Subjective improvement, frequency of artificial tear application, tear function parameters (break up time, Schirmer test without local anaesthesia), vital staining (fluorescein and rose bengal staining) as well as impression cytology of the bulbar conjunctiva were evaluated before treatment, 1 week, 1 month, and 3 months after treatment. Results: A reduction in subjective symptoms, frequency of artificial tear substitute application, and an improvement in certain tear film and ocular surface factors could be observed in both groups. A stronger positive influence was seen after application of iodide with current (iontophoresis), as observed in a distinct improvement in break up time, fluorescein and rose bengal staining, and in a longer duration of this effect compared with the non-current group. No significant change in Schirmer test results and impression cytology were observed in both groups. Conclusions: Iodide iontophoresis has been demonstrated to be a safe and well tolerated method of improving subjective and objective dry eye factors in patients with ocular surface disease.