The technique for split-thickness skin graft harvest varies among surgeons. Even though there is scientific evidence that the subcutaneous injection of modified tumescent solution reduces blood loss during burn surgery, the technique has not been unanimously adapted because of, in part, fear of healing retardation. This study prospectively examines the effect of tumescent injection on donor site perfusion, healing, and pain. Ten burn patients in need of grafting with a need for two distinctly different donor sites were included. During the grafting procedure, the two donor areas were randomly assigned to receive either modified tumescent solution or warm sterile saline solution subcutaneously before skin graft harvest with a dermatome. Perfusion, pain, pruritus, and donor site healing were measured, and a follow-up evaluation on scar quality was performed. Baseline perfusion on day 1 was significantly less in the donor site injected with modified tumescent solution (62.26 vs 95.71 perfusion units; P = .031), whereas the response to heat was similar in both sites. The physiologic response to injury (hyperemia) on days 2 and 3 was not suppressed in the modified tumescent group. Pain reported on day 1 was 2.38/10 in the tumescent site and 3.38/10 in the saline site (P = .21). On all other days, measurements showed no difference between the two sites. Donor sites healed in an average of 16.1 days with modified tumescent solution and in 16.4 days with saline. Late follow-up showed no difference in scar quality. The subcutaneous injection of modified tumescent solution before split-thickness donor site harvest has no adverse effect on donor site perfusion past day 1 or donor site healing. The addition of a local anesthetic may decrease pain for 24 hours postoperatively, but the difference in this study group was not significant. This technique should be universally recommended.