Purpose <p>To assess safety and outcomes of stereotactic CT-guided microwave ablation (MWA) for hepatocellular carcinoma (HCC) in patients with transjugular intrahepatic portosystemic shunts (TIPS) versus a matched control group without TIPS.</p> Materials and Methods <p>Retrospective matched case–control study of cirrhotic patients with HCC treated with stereotactic CT-guided MWA. TIPS patients were matched 1:1 to controls using hierarchical matching based on Child–Pugh class, number of treated tumors, MELD score, tumor diameter, and ablation date. Primary endpoints were primary technique efficacy (PTE), local tumor progression (LTP), 30-day complications, and 30-day all-cause mortality. Secondary endpoints were 12-month Kaplan–Meier estimates for progression-free survival (PFS), hepatic decompensation-free survival (HDFS), and overall survival (OS), compared using log-rank tests.</p> Results <p>46 patients (23 TIPS, 23 controls) with 62 index lesions were analyzed. PTE was achieved in 30/31 lesions (96.8%) in both groups. Among lesions with PTE, LTP occurred in 1/30 lesions (3.3%) in the TIPS group and 0/30 lesions (0%) in controls. Within 30&#xa0;days, two major complications occurred in the TIPS group and one in the control group; no 30-day deaths occurred. Observed 12-month estimates did not differ significantly between groups for PFS (52.4% vs. 46.0%, <i>p</i> = 0.876), HDFS (71.8% vs. 76.9%, <i>p</i> = 0.519), or OS (91.1% vs. 90.0%, <i>p</i> = 0.903). Child–Pugh A was associated with higher HDFS than Child–Pugh B (95.8% vs. 50.2%, <i>p</i> = 0.001).</p> Conclusion <p>Stereotactic CT-guided MWA of early-stage HCC appears feasible in carefully selected patients with TIPS, warranting further evaluation in larger cohorts.</p> Level of Evidence <p>3b.</p> Graphical abstract <p></p>