Applying skin protective cream and the wearing of gloves?—A randomized controlled experimental study Glove occlusion might enhance skin sensitivity to a subsequent detergent challenge (occlusion effect). Thus, some skin protection creams (PC) claim to protect against this effect of occlusion, and are recommended to be used before wearing liquid‐proof gloves.</jats:p></jats:sec><jats:sec><jats:title>Objectives</jats:title><jats:p>To evaluate the effect of PC applied prior to glove occlusion on the ‘occlusion effect’—refers to increased susceptibility of the skin to a model detergent.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>One hundred and eleven volunteers were enrolled in a single‐blind, randomized study. Seven PCs were applied before glove occlusion over 7 days (D1–D7). After sodium lauryl sulphate (SLS) challenge, we compared the irritation between the areas treated with PC and occlusion alone. Clinical scoring and bioengineering methods (capacitance, transepidermal water loss [TEWL], and colourimetry [erythema]) were used to quantify the irritant reactions.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>After 1 week of occlusion and PC application, we did not observe significant changes in TEWL, nor in erythema, whereas skin hydration raised in three cream‐treated areas. On day 10, after a challenge with SLS, some products significantly aggravated the skin irritation as compared to occlusion alone.</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>The ‘occlusion effect’—shown as higher skin susceptibility to a model detergent—was not mitigated by PCs when applied prior to glove occlusion. On the contrary, some PCs might have negative effects on skin barrier function and augment such sensitivity. 88 5 372-382 372-382 Wiley 1