Identification of receptors and processes involved in the development and transmission of pain has led to the use of new tools and methods that provide promising and more effective approaches to pain control. Anesthetic substances inhibit generation and propagation of the action potential, with the resting potential of nerve fibers being slightly affected. The article presents the results of an open, randomized, comparative study of the efficacy and safety of local anesthetics used for skin anesthesia in surface surgery. Purpose. The study purpose was to evaluate and compare the efficacy and safety of local anesthetics applied both with and without an occlusive dressing. Material and methods. The study included 152 patients randomized into three groups, depending on the used drug and the method of its application. All participants required skin anesthesia for surface surgery used in dermatology and cosmetology. The efficacy and safety were assessed at primary and secondary endpoints. Results. There were no significant differences in the efficacy among individual groups. Evaluation of vital functions, chemistry blood panel, complete blood count, and clinical urinalysis revealed no negative changes. The revealed deviations of laboratory indicators were regarded as clinically insignificant.