Wrist pain is common. People with persistent pain commonly undergo arthroscopic investigation. Little is known about the prognosis or prognostic factors for these patients. The purpose of the study was to evaluate prognosis and prognostic factors for pain and functional disability in patients with persistent wrist pain who proceed to arthroscopic investigation. The study design used was a prospective cohort study. One hundred and five consecutive participants who underwent arthroscopic investigation for undiagnosed wrist pain for at least four-week duration were recruited. Patient-rated wrist and hand evaluation (PRWHE) scores were determined at baseline (before arthroscopy) and one year after arthroscopy. One-year follow-up data were obtained for 97 (92%) of 105 participants. Mean PRWHE total score declined from 49 of 100 (standard deviation [SD] 18.5) at baseline to 26 of 100 (SD 20.4) at one year. Two prognostic factors were identified: baseline PRWHE and duration of symptoms. These factors explained 19% and 5% of the variability in the final PRWHE score, respectively. Results of provocative wrist tests and arthroscopic findings did not significantly contribute to prognosis in this cohort. This study provides the first robust evidence of the prognosis of persistent wrist pain. Participants who underwent arthroscopic investigation for persistent wrist pain improved on average by approximately 50% at one year; however, most continued to have some pain and disability. Duration of pain and PRWHE at baseline explained 24% of the one-year PRWHE score. Level of Evidence: Level 2.