Refrigerant sprays have been widely used to reduce pain in the office setting. However, more recently, their use has been limited by both concern regarding flammability and questions of bacterial contamination. We investigated the microbiological effect of 1,1,1,3,3 pentafluoropropane and 1,1,1,2-tetrafluoroethane when sprayed after povidone-iodine application in 50 volunteers. In 50 volunteers, 3 cultures were taken (1) at time 0 before antiseptic application, (2) after povidone-iodine topical antiseptic, and (3) after spraying with vapocoolant. Cultures at 3 time intervals were analyzed in a blinded fashion, and Gram stains obtained when cultures were positive. Bacterial growth was found in 98% of cultures taken before antiseptic was applied (Group 1), in 28 cultures (56%) after povidone-iodine was applied, and in 24 cultures (48%) after spraying with vapocoolant. There was a statistically significant difference found between Group 1 (no antiseptic) and both Group 2 (after antiseptic but before vapocoolant) and Group 3 (after vapocoolant) (p < .001). The topical antiseptic povidone-iodine significantly reduces skin colonization when compared with unprepared skin (p < .001). The vapocoolant 1,1,1,3,3 pentafluoropropane and 1,1,1,2-tetrafluoroethane is sprayed on skin prepared with povidone-iodine; there is no statistically significant increase in bacterial colonization.