Introduction Human in vivo models of skin damage were often used in research of cutaneous disorders. The most commonly used models were tape‐stripping as mechanical, sodium lauryl sulphate‐induced irritation as chemical and ultraviolet radiation as physical damage model. In regard to differences between models, they were expected to have different responses to damage and recovery, with unique skin parameters’ changes over time. Objective The aim was to compare skin parameters in three different skin damage models on the same anatomical location, with and without topical treatment. Methods Four test sites on each forearm were randomly assigned to three skin damage models with the fourth sites on each forearm chosen as a control, undamaged site. Skin parameters were assessed using non‐invasive methods. Results Sodium lauryl sulphate irritation caused the strongest damage with delayed reaction to the irritant. Tape stripping leads to highest initial skin barrier disruption but afterwards it showed the fastest skin recovery. Ultraviolet radiation did not affect skin barrier function, but it elevated skin erythema and melanin level. Tested preparation did not lead to changes in measured parameters. Conclusion The skin of the participants had different response to three skin damage models with distinct changes of skin parameters and recovery. The trial was registered at ClinicalTrials.gov under the identifier NCT03783819.