Background <p>The radial forearm free flap (RFFF) is widely used in microvascular reconstructions. However, donor site morbidity remains a concern, with complications such as wound healing issues, functional impairments, and aesthetic concerns. While both full-thickness skin grafts (FTSG) and split-thickness skin grafts (STSG) are commonly used for donor site closure, there is insufficient evidence to determine which technique leads to fewer complications. This study aims to systematically compare FTSG and STSG in RFFF donor site closure.</p> Methods <p>We searched six databases and four clinical trial registries up to 1 March 2025. We focused on studies comparing FTSG and STSG. Primary outcome was the incidence of wound complications. Secondary outcomes included functional and aesthetic impairment. Risk of bias was assessed using the Risk Of Bias In Non-Randomized Studies—of Interventions (ROBINS-I) and quality of the evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.</p> Results <p>Fifteen studies were analyzed, involving 933 donor site closures. No RCTs met our inclusion criteria. Meta-analysis comparing FTSG versus STSG revealed no significant differences in major wound complications (<i>RR</i> 0.43; 95% <i>CI</i> 0.11 to 1.70; <i>p</i> = 0.23) and minor wound healing complications (<i>RR</i> 0.83; 95% <i>CI</i> 0.60 to 1.13; <i>p</i> = 0.23), with the evidence graded as low to very low certainty.</p> Conclusion <p>Current evidence does not conclusively favor either FTSG or STSG for radial forearm free flap donor site closure regarding wound, functional, or aesthetic outcomes. Future well-designed RCTs are needed to provide higher-quality evidence to guide clinical decision-making. Until more robust evidence becomes available, the optimal skin graft choice should be guided by patient-specific factors, surgical considerations, and donor site characteristics.</p> Systematic review registration <p>PROSPERO CRD42023351903.</p>