Objective To investigate the relationship between microRNA-183-5p (miR-183-5p) levels and rebleeding after transjugular intrahepatic portosystemic shunt (TIPS) in cirrhosis patients with esophageal and gastric variceal bleeding.Methods A total of 178 cirrhosis patients with esophageal and gastric variceal bleeding treated with TIPS in the 3201 Hospital Affiliated to Xi’an Jiaotong University Health Science Center from February 2017 to October 2020 were prospectively selected. The patients were then divided into rebleeding group and non-rebleeding group. The levels of miR-183-5p prior to TIPS (T₁), 24 h after TIPS (T₂) and 7 days after TIPS (T₃) were measured by quantitative real-time polymerase chain reaction (qRT-PCR). The occurrence of rebleeding after TIPS was followed up and the relationship between miR-183-5p and the occurrence of rebleeding after TIPS was analyzed.Results There was no difference in the gender, age, the cause of cirrhosis, the distribution of Child-Pugh classification, the platelet count, prothrombin time, and the international normalized ratio between the two groups. The levels of albumin, blood sodium and blood calcium in the rebleeding group were lower than those in the non-rebleeding group (P < 0.05). The inner diameter of portal veins and the frequency of severe esophageal varices in the rebleeding group were higher than those in the non-rebleeding group (P < 0.05). The levels of miR-183-5p at T₁, T₂, and T₃ were compared between the two groups, and the repeated-measures analysis of variance demonstrated that the levels of miR-183-5p were different among the time points (P < 0.05) and between the groups (P < 0.05). The change trends of miR-183-5p levels were also different between the two groups (P < 0.05). The area under the receiver operating characteristic (ROC) curve [0.827 (95% CI: 0.768, 0.886) ] and the sensitivity [74.55% (95% CI: 61.00, 85.30) ] of the miR-183-5p level at T₁, and the specificity of the miR-183-5p level at T₃ [88.62% (95% CI: 81.60, 93.60) ], were the highest for determining the occurrence of rebleeding after TIPS in cirrhosis patients with esophageal and gastric variceal bleeding (P < 0.05). The multivariable Logistic regression analysis revealed that blood sodium > 136.62 mmol/L [O^R = 0.177 (95% CI: 0.073, 0.429)], blood calcium > 2.07 mmol/L [O^R = 0.386 (95% CI: 0.160, 0.928)] and the miR-183-5p level at T₁ > 1.19 [O^R = 0.079 (95% CI: 0.029, 0.216) ] were independent protective factors for rebleeding after TIPS in cirrhosis patients with esophageal and gastric variceal bleeding (P < 0.05), and that the inner diameter of portal veins > 1.30 cm [O^R = 3.094 (95% CI: 1.290, 7.421) ] and severe esophageal varices [O^R = 8.342 (95% CI: 2.086, 33.367) ] were independent risk factors for rebleeding after TIPS in cirrhosis patients with esophageal and gastric variceal bleeding (P < 0.05). The concordance index (C-index) of model A (including blood sodium, blood calcium, inner diameter of portal veins and severity of esophageal varices) was 0.771, and the mean absolute error of model A was 0.025. The C-index of model B (including blood sodium, blood calcium, inner diameter of portal veins, severity of esophageal varices and the miR-183-5p level at T₁) was 0.867, and the mean absolute error of model B was 0.028. The net benefit of model B to determine the occurrence of rebleeding after TIPS in cirrhosis patients with esophageal and gastric variceal bleeding was higher than that of model A.Conclusions High miR-183-5p levels before TIPS in cirrhosis patients with esophageal and gastric variceal bleeding suggest a low risk of rebleeding. The prediction model established based on the level of miR-183-5p is valuable in determining whether rebleeding occurs after TIPS in cirrhosis patients with esophageal and gastric variceal bleeding.