The ability of topical metal-containing agents (MCAs) to enhance radiation dermatitis remains controversial. In the present study, we evaluated increases in surface doses associated with topical agents at different application thicknesses and with MCAs versus non-metal containing agents (NMCAs). We assessed two clinically available MCAs, zinc oxide ointment (ZOO) and silver sulfadiazine cream (SSDC), and eight NMCAs. Surface doses were measured using a Markus chamber placed on a polystyrene phantom. To evaluate the role of application thickness, each agent was applied to the chamber in oil-slick (<0.1-mm), 1-mm and 5-mm layers prior to irradiation of a 10 × 10 cm field with 4-, 6- and 10-MV X-ray beams. The surface dose enhancement ratio (SDER) was calculated as the ratio of the surface dose with an agent to the dose without an agent. The SDER values for the eight NMCAs, ZOO and SSDC at an oil-slick thickness were 101.6-104.6% (mean: 103.3%), 104.5% and 105.0%, respectively, using a 6-MV X-ray beam. The corresponding values at a 1-mm thickness were 196.8-237.8% (mean: 215.7%), 229.3% and 201.4%, respectively, and those at a 5-mm thickness were 342.2-382.4% (mean: 357.9%), 357.1% and 352.6%, respectively. A similar tendency was found using 4- and 10-MV X-ray beams. The lack of a significant difference in surface dose enhancement between MCAs and NMCAs, particularly when applied in oil-slick layers, suggests that MCAs do not need to be avoided or applied in a restricted manner during radiotherapy for dosimetric reasons.