Although many patients with hepatocellular carcinoma (HCC) undergo transjugular intrahepatic portosystemic shunt (TIPS) creation, with significant resultant hemodynamic changes, the literature contains few studies on the effectiveness of transarterial chemoembolization (TACE) in patients with TIPS. The purpose of this study is to evaluate the effectiveness of TACE for HCC in patients with TIPS versus those without TIPS. All patients who underwent TIPS at our institution from 2008 to 2012 were identified via records review; 12 of these patients also had HCC and were treated with TACE. A matched control group of 22 patients treated with TACE without TIPS during the study period was created, based on demographic characteristics, MELD scores, and tumor size. Post-TACE imaging was systematically evaluated and compared to pre-TACE imaging by modified response evaluation criteria in solid tumors (mRECIST). Time to progression, survival, and transplant rate were noted. No difference was seen between TIPS and control groups in immediate post-TACE complete response rate (45% vs. 55%, p= 1.0) and combined response rate (both complete and partial) (67% vs. 82%, p = .41). Mean follow-up intervals were 382 days (TIPS) and 465 days (control). Mean time to progression (local recurrence) was significantly shorter in the TIPS group than the control group: 135 days (SD 56) vs. 315 days (SD 167), p = 0.013. Overall survival was lower in the TIPS group than in the control group (75% vs. 91%), suggesting a trend but not statistically significant (p = 0.32). Transplant rates were similar in the TIPS and control groups, 27% vs. 25%, respectively. Although immediate post-TACE complete response rate by mRECIST was similar in patients with TIPS compared with those without TIPS, patients with TIPS demonstrated significantly faster local progression and a trend towards shorter overall survival, which may indicate decreased effectiveness of TACE after TIPS.