Introduction: Human in vivo models of skin damage are often used to test the effects of different topical treatments. Commonly used model is irritant contact dermatitis induced by chemical irritant, sodium laurylsulphate (SLS). There is no uniform approach to SLS testing, as different research groups use significantly different variations of the model, especially in regards to anatomical location where testing was conducted. Other commonly used skin damage models include tape-stripping as mechanical and ultraviolet radiation as physical skin damage model. Objective: The aim was to investigate differences in skin response to acute irritation induced by SLS and skin recovery between forearms and upper back, as well as to compare skin parameters in three different skin damage models on the same participants and anatomical location, in the same research conditions. Materials and Methods: Two randomized, controlled trials were conducted. In the trial 1, the skin irritation was induced using SLS on the forearms and upper back of the participants, with sham irritation, using water instead of SLS, as control. In the trial 2, the three skin damage models were induced on test sites on participants’ forearms. Changes in skin parameters and skin recovery in both trials were assessed using non-invasive bioengineering methods, with and without topical treatment. Results: In the trial 1, the skin of the upper back had significantly stronger reaction to irritant, as well as higher skin recovery rates. In trial 2, three tested skin damage models led to different changes of the skin parameters. Irritation by SLS induced the strongest skin damage and also showed delayed reaction to the irritant. The strongest initial barrier disruption was noted after tape-stripping. Also, tape-stripped skin had the highest recovery rates. Ultraviolet radiation did not have any effect on skin barrier function and only changed skin erythema and melanin values. Measured parameters were not improved by topical treatments in neither trial. Conclusion: The skin’s reaction to irritant and recovery was dependent on anatomical location. Three tested models had distinctive responses to skin damage and recovery.