BACKGROUND W/O emulsions improve the stratum corneum barrier, while microemulsions tend to compromise it. We, therefore, were interested to explore the effects of O/W emulsions on the stratum corneum barrier. METHODS Aqueous Cream BP 2001, Clioquinol Cream BP 1999 without clioquinol, Nonionic Hydrophilic Cream DAB 2001 without glycerol, Hydrophilic Skin Emulsion Base NRF S. 25., point of time 2001, without glycerol, and Base Cream DAC were tested versus untreated controls in 29 healthy volunteers for 7 days. Outcome measures included transepidermal water loss (TEWL), skin redness (chromametry a*-value) and erythrocyte circulation in the subpapillary vessels (laser Doppler). Barrier compromise was subsequently explored by performing the hydrocortisone blanching test using Hydrocortisone Cream 0.5% NRF 11.36. (outcome measure: a*-value) in 15 subjects and the sodium lauryl sulfate (SLS) irritation test (outcome measures: TEWL, a*-value, laser Doppler) in 14 subjects. RESULTS Pretreatment with the test emulsions produced increases in TEWL (statistically significant for all test emulsions), a*-value (statistically significant for Aqueous Cream BP 2001 and Base Cream DAC), and laser Doppler value (statistically significant for all emulsions except Base Cream DAC). Hydrocortisone penetration was statistically significantly increased with all test emulsions versus untreated contols. SLS irritation was mostly statistically significantly increased versus untreated controls when analyzing the study endpoint-baseline difference. CONCLUSIONS O/W emulsions may compromise the stratum corneum barrier and improve drug penetration.