Objective To evaluate the clinical, functional and aesthetic outcomes for radial forearm free flap (RFFF) donor sites covered with amniotic membrane (AM). Material and methods The healing process of patients with RFFF donor sites covered with AM was prospectively followed for 1 year. Additionally at the 12-month evaluation, objective scoring systems were used to assess the aesthetic (Vancouver scar scale, VSS: range 1-13) and functional outcome (skin sensibility, hand/wrist functionality [goniometer], grip strength [score 1 = excellent, 5 = poor]). By using a subjective rating system (score 1 = excellent, 5 = poor), the patient-reported aesthetic and functionality outcome was correlated with objective data analysis. Results Twenty-one out of 23 patients were followed for 12 months (dropout: 2 patients at 3 months). In 17/23 (73.9%) patients RFFF defect covered with AM showed an uneventful healing period (< 3 months). Prolonged healing periods (> 3 months < 6) for 6 patients (26.1%) were attributed to wound infections (4×), seroma (1×) and inflammation (1×). At the 1-year evaluation, there was a significant (p < 0.01) correlation between subjective (2.0 ± 0.71) and objective aesthetic scores (VVS 3.74 ± 2.18), and a successful grip strength (score 1.67 ± 0.86); however, thumb hyposensibility in 76.2% was seen. A high body mass index (BMI) was in conjunction with a negative (p = 0.012) and the use of antihypertensive medications provided positive effects (p = 0.041) on the aesthetic outcome. Conclusion RFFF donor site defects covered using AM show excellent clinical, aesthetic and functional outcome representing patient comorbidities (BMI, antihypertensive drugs) might affect the aesthetic outcome. Clinical relevance In relation to the excellent outcomes found, the use of AM offers an alternative treatment procedure for RFFF defect covering.