STUDY DESIGN.: Cohort study. OBJECTIVE.: The aim of this study was to explore the association between blood-spinal cord barrier (BSCB) markers and other factors associated with an unfavorable outcome among patients with post-traumatic syringomyelia (PTS) who achieved successful intradural adhesion lysis (IAL). SUMMARY OF BACKGROUND DATA.: Only approximately half of PTS patients receiving IAL have a favorable outcome. PATIENTS AND METHODS.: Forty-six consecutive patients with PTS and 19 controls (CTRL) were enrolled. All PTS patients underwent physical and neurological examinations and spinal magnetic resonance imaging before and 3 to 12 months after IAL. All patients underwent myelography before surgery. BSCB disruption was detected by increased intrathecal and serum concentrations of albumin, immunoglobulin (Ig)G, IgA, and IgM. A multivariable analysis was performed with a logistic regression model to identify factors associated with unfavorable outcomes. Receiver operating characteristic curves were calculated to investigate the diagnostic value of biomarkers. RESULTS.: The ages and general health of the PTS and CTRL groups did not differ significantly. QAlb, IGAQ, IGGQ, and IGMQ was significantly higher in PTS patients than in controls (P=<0.001). The degree of intradural adhesion was significantly higher in the unfavorable outcome group than in the favorable outcome group (P<0.0001). QAlb, immunoglobulin (Ig)AQ, IGGQ, and IGMQ was significantly correlated with clinical status (R=−0.38, P<0.01; R=−0.47, P=0.03; R=−0.56, P=0.01; R=−0.43, P=0.05, respectively). Higher QAlb before surgery (odds ratio=2.66; 95% CI: 1.134–6.248) was significantly associated with an unfavorable outcome. The receiver operating characteristic curve analysis demonstrated a cutoff for QAlb higher than 10.62 with a specificity of 100% and sensitivity of 96.3%. CONCLUSION.: This study is the first to detect increased permeability and BSCB disruption in PTS patients. QAlb>10.62 was significantly associated with unfavorable clinical outcomes following intradural decompression. LEVEL OF EVIDENCE.: Level III—prognostic.