BACKGROUND Sinusoidal obstructive syndrome (SOS) is a disease that damages hepatic sinusoidal endothelial cells, resulting in progressive occlusion and fibrosis of the lobular central vein and the occurrence of intrahepatic sinusoidal portal hypertension. However, SOS after liver transplantation (LT) is uncommon and potentially fatal. Here, we report a rare case of second-time recurrence of SOS after liver retransplantation (rLT). CASE SUMMARY A 22-year-old woman received a living donor LT due to SOS. Four years later, she developed abdominal distention and ascites with no apparent cause. She was diagnosed with recurrence of SOS and underwent rLT. But 2 mo post rLT, the patient suffered from aggravated jaundice and ascites again. She was diagnosed with second-time recurrence of SOS post-rLT according to computed tomography and liver pathology. After treatment with warfarin anticoagulation and immunosuppressant conversion, she gradually recovered with improvement of liver function and liver pathology. During the 17-mo follow-up period, she was in good condition with normal liver function and no ascites. CONCLUSION SOS can be a recurrent disease after LT, and autoimmune antibody and genetic sequencing should be screened before LT. For susceptible patients, anticoagulant drugs should be used for an extended period, and tacrolimus or other pathogenic agents should be avoided. Early diagnosis and treatment can improve the prognosis of patients and avoid graft failure or death.