Abstract Introduction The scalp is an appealing donor site for split-thickness skin grafting (STSG) of burns due to its concealment upon hair regrowth and healing potential; however, it is often reserved for massive burns with limited donor sites. This study aims to understand scalp donor site (SDS) outcomes and complications to elucidate viability of the SDS as a first-line option for coverage of burns. Methods A systematic review across five databases was conducted. Original research reporting cohort outcomes of STSG coverage of burns using the SDS was included. Donor site healing time, graft thickness, graft take, and complications were analyzed. Thereafter, a retrospective chart review of patients who had SDS-STSGs for burns from 2010–2018 was done. Outcomes and complications were compared to non-SDS-STSGs (NSDS-STSGs) in criteria-matched controls. Results Systematic Review: 1489 articles were reviewed. 15 cohort studies met inclusion criteria, yielding 1761 patients who has SDS-STSG (mean age=17 yrs, mean TBSA=37%). Alopecia and folliculitis occurred in 5% and 3% of patients, respectively; folliculitis was associated with certain hair types. Other complications (eg. hypertrophic scarring, hair transfer) were seen in less than 1.5% of patients. Rapid donor site healing times (mean=8 days) and capacity for re-harvest (mean=2 harvests/patient) were noted. Retrospective Review: 30 patients underwent grafting with SDS-STSGs, 23 of whom also received NSDS-STSGs and were thus self-controls; criteria-matched controls were found for the remaining 7. Graft thickness and graft take did not differ between SDS and NSDS groups, while donor site healing time was faster for SDSs vs NSDSs (9 vs 11 days, p=0.02). SDS complications included: alopecia (n=2), delayed healing (3), and folliculitis (1). NSDS complications included: delayed healing (n=1), dyspigmentation (2), and hypertrophic scarring (3). These complications could not be attributed to age, ethnicity, graft thickness, number of graft harvests, comorbidity burden, TBSA, or inhalational injury status. Conclusions The scalp donor site may represent a viable first-line option for split-thickness skin grafting of burns. Our cohort suggests that scalp donor sites pose comparable risks to non-scalp donor sites. Further studies elucidating the role of hair type in SDS-STSG complications are required to optimize outcomes with patient-specific donor site selection. Applicability of Research to Practice In select patients, the scalp may be considered as a first-line donor site for split-thickness skin grafting of burns, with potentially faster donor site healing time and comparable risks to non-scalp donor sites. Some scalp-specific complications may be linked to differences in hair type.