Chelating agents in protective barrier creams have often been used in the prevention of allergic contact dermatitis to nickel. In a pilot study, we demonstrated the preventive effect of 10% diethylenetriaminepentaacetic acid (DTPA) in an oil-in-water emulsion in nickel-sensitized patients. Now we reproduced these results in a randomized, double-blind study. Additionally, we investigated the efficacy of the barrier cream in other clinically relevant metal allergies. Individuals sensitized to various metals had a significant decrease in positive patch test reactions after pre-treatment with the DTPA-cream: 2.5% nickel sulfate (24/28 positive without pre-treatment versus 1/28 with pre-treatment; p<0.0001), 5% nickel sulfate (30/32 versus 15/32; p=0.0003), 1% cobalt chloride (19/20 versus 6/20; p=0.001) and 5% copper sulfate (13/14 versus 5/14; p=0.02). However, the cream had no protective effect with 1% palladium chloride (17/23 versus 16/23) and with 0.5% potassium dichromate (9/13 versus 7/13). We conclude that the DTPA-cream clearly abrogates positive patch test reactions in nickel-, cobalt- and copper-sensitized subjects and that it may therefore be helpful in the management of allergic contact dermatitis.