Distal injuries in human fingertips can regenerate almost fully, yet the process of human fingertip regeneration has hardly been characterized on a cellular and molecular level. A silicone finger cap, comprising a puncturable reservoir, was used to treat 22 human fingertip amputations. In all patients, subcutaneous tissue, nailbed and skin regenerated with excellent outcomes. Through the clinical assessment of the wounds, the regenerative process was divided into four distinct phases. Proteomic data from wound fluid samples collected at regular intervals, confirmed robust and unbiasedly distinct proteomic signatures, characteristic processes, and active regulatory networks in each phase. Moreover, this human dataset provides important insights, showing clear divergences from findings in regenerative animal models. The longitudinal and comprehensive analysis presented here unveils the complex orchestration of four clinically and proteomically-distinct phases of human fingertip regeneration. Further analyses of this proteomic data will allow for the identification of candidates orchestrating human fingertip regeneration and serving as a framework for comparative and regenerative medicine studies. This clinical trial was registered at ClinicalTrials.gov Identifier: NCT03089060 on March 17, 2017.