External root resorption may develop following intracoronal bleaching with hydrogen peroxide. The preventive effect of different base materials on the radicular penetration of H2O2 during intracoronal bleaching was assessed. Seventy-two bovine teeth and 20 human teeth were bleached with 30% H2O2. The bovine teeth were divided into four groups and the root canals filled with either IRM, zinc oxideeugenol, composite resin, or glass ionomer. The radicular H2O2 penetration of each group at different layer thickness was compared. The experiment with the human teeth was performed in three stages. In the first stage no protective base was used. In the second stage IRM was placed to the cementoenamel junction level. In the third stage the IRM layer was removed 0.5 mm below the cementoenamel junction. None of the materials tested in the bovine teeth showed H2O2 penetration with a base thickness of 2 mm. When the base thickness was reduced to 1 mm, several teeth showed H2O2 penetration; however, there was no significant difference among the materials tested. When the base thickness was reduced to 0.5 mm, the H2O2 penetration in each group increased. A statistical difference was found between the composite and the glass ionomer (p < 0.05). The results for the human teeth showed that IRM layer placed at the cementoenamel junction level significantly reduced the radicular H2O2 penetration as compared with teeth where the IRM was either placed 0.5 mm below the cementoenamel junction or not placed at all (p < 0.01). It is therefore recommended that a protective base be placed to the cementoenamel junction level before intracoronal bleaching to prevent possible H2O2 hazards.