BACKGROUND Various studies have investigated structural knee changes after running, with conflicting results. PURPOSE To perform a systematic review of acute changes in knee structures as detected by magnetic resonance imaging (MRI) after running and assess the reversibility of these changes. STUDY DESIGN Systematic review. METHODS A systematic literature search in Medline, Cochrane, Embase, and Scopus was performed. Articles that fulfilled predefined inclusion criteria were included and systematically reviewed according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement. RESULTS A total of 19 studies were included in this review. All studies performed standard knee MRI; 6 studies additionally performed T1ρ and T2 mapping. Sixteen studies assessed cartilage or meniscal morphological changes. Ten found no significant morphological changes after running. Six studies showed significant changes at the first follow-up. Six performed a second follow-up. Five showed no change compared with baseline and the first follow-up, and 1 showed a significant recovery compared with the first follow-up and no significant difference compared with baseline. Five of the 6 studies performing T1ρ and T2 mapping found significant changes in T2 and T1ρ values at the first follow-up. Three performed a second follow-up. Two found a significant recovery of T2 but no recovery of T1ρ. One study did not find a significant change compared with baseline. Ten studies assessed the patellar tendon, ligaments, synovial fluid, or subchondral bone. Changes at the first follow-up were not significant. A second follow-up was performed in 5 studies. All studies discovered recovery from the first follow-up. CONCLUSION These data suggest that healthy athletes who have no risk factors for degenerative joint disease may present fleeting quantitative alterations after running. No irreversible, qualitative harmful effects seemed to occur, with the exception of persistent T1ρ elevation representing a proteoglycan depletion. Whether T1ρ changes need more than 3 months to recover or represent permanent structural damage remains to be investigated.