Severe atopic dermatitis (AD) is observed in 10-15% of all adult AD patients, and the number of severe, often disabling, cases with insufficient efficacy of conventional treatment methods increases over the years. The objective of this study was to evaluate the efficacy and safety of 0.1% tacrolimus ointment (Protopic) in the combined therapy of patients with severe AD, resistant to other therapies. The study group included 29 patients who gave a voluntary consent to participate in the study; the control group included 12 patients who rejected the use of tacrolimus ointment for various reasons. Clinical monitoring of the patient's status, including the definition of the SCORAD index and the degree of anxiety and depression according to the HADS scale, was performed before therapy, on the 14th and 28th days of treatment. Tacrolimus ointment 0.1% was applied 2 times a day until the clinical effect was achieved (but not less than for 14 days), and further 2 times a week at the areas of the former or frequent lesions during exacerbations. Control group patients continued receiving topical corticosteroids and indifferent ointments. More than a half of patients in both groups have been suffering from AD for more than 20 years; the erythematous-squamous clinical form with lichenification prevailed. The average SCORAD index was 72.8 in the study group, and 73.1 in the control group; the HADS index was 15.2 and 15.0, respectively. After 14 days, the dynamics of the SCORAD and HADS indices in the study group was 50.8 and 38.8%, respectively. On the day 28, the SCORAD index decreased 3.2 times, while the HADS index (degree of anxiety and depression) decreased sixfold. In 86.2% of cases, the patients in this group were satisfied with treatment results; in 96.6% of patients, the tolerability was good. Thus, the use of 0.1% tacrolimus ointment (Protopic) to treat patients with the dermatological process that was resistant to other treatments can be considered to be highly effective and comfortable to be used.