Healing after Achilles tendon rupture (ATR) is protracted with high individual variation and unsatisfactory outcome. Biomarkers prognostic of healing are unknown while physical and mechanical factors are used for predicting long-term healing outcomes in clinics today. The present study was designed to investigate the proteomic profile of healing, identify potential biomarkers, and asess the association with the patient's long term outcomes after ATR. Using quantitative Mass Spectrometry (MS) analysis, 1423 proteins in healing and contralateral healthy Achilles tendon from 28 ATR patients were quantified. Comparing healing and healthy protein profiles, we identified 821 overlapping proteins. Further analysis revealed 390 up-regulated and 17 down-regulated proteins in healing compared to the healthy contralateral side,mainly related to extracellular matrix organization, inflammation, and reduced exocytosis and metabolic pathways. Our analysis based on clinical parameters, identified complement factor D (CFD) as the most reliable predictive biomarker of successful tendon healing.Our findings identidied identified prognostic biomarkers and potential therapeutic target for improving tendon or ligament injuries.