Many rehabilitative attempts have been made to prevent or reduce residual deficits in patients with established and long-term facial palsy (FP). In many clinical settings in-situ injection of collagen-based medical devices have been demonstrated to provide nutritional support for tissues. To test the effectiveness of a collagen-based treatment for patients complaining of long standing FP, who are following a proprioceptive neuromuscular facilitation protocol (Kabat method) (group A), compared to a FP group only undergoing the Kabat method (group B). Randomised controlled trial. Tertiary referral outpatient center and University Hospital. Forty-one patients with a medical diagnosis of long-term unilateral peripheral FP. Twenty-one Group A patients were compared, after randomization, to nineteen matched group B patients after 8 weeks of treatment. The outcomes were electromyographic findings, validated questionnaires (Facial Disability Index, FDI and General health-related quality of life assessment, QOL) and clinical grading (House-Brackmann, HB, and synkinesis grading scale). A correlation analysis was performed between pre-/post-treatment differences (Δ) in outcome and clinical-demographic measures. A significant within-subjects improvement, both in electrophysiological and questionnaire scores, was found in both groups. When compared with group B, group A patients exhibited a significant reduction of post-treatment polyphasic potentials of voluntary activity of orbicularis oculi (P=0.017) and oris (P=0.015) and a significant increase in post-treatment duration of voluntary activity of orbicularis oris (P=0.018). Group A subjects demonstrated a significant improvement in questionnaire subscales regarding overall disease perception. Although positive correlations between the ∆FDI and ∆percentage of polyphasic potentials of voluntary activity were found in both groups, negative correlations in group A were found between disease duration and ∆duration of voluntary activity of orbicularis oculi and oris. The combination of physical rehabilitative procedures with in-situ collagen injections, possibly acting in redirecting the phenomena of reinnervation/reorganization, demonstrated encouraging results in patients affected by long term FP. In-situ collagen injection could be a safe option enlarging the 'window of opportunity' to improve the voluntary muscle contraction pattern and general and specific disability referred by patients affected by long standing FP.