Purpose: To compare survival outcomes of patients with single medium-sized hepatocellular carcinomas (HCCs) who underwent treatment with transarterial chemoembolization, radiofrequency (RF) ablation, or a combination of the 2 therapies. Materials and Methods: Between 2000 and 2016, 538 patients underwent combined chemoembolization and RF ablation (n = 109), chemoembolization alone (n = 314), or RF ablation alone (n = 115) as first-line treatment for a single medium-sized (3.1-5.0 cm) HCC. Baseline demographic data (age, sex, etiology, Eastern Cooperative Oncology Group performance status, presence of liver cirrhosis, and serum bilirubin, albumin, and a-fetoprotein levels) were similar among groups except for Child-Pugh class, albumin level, and tumor size. Propensity-score analysis with inverse probability weighting (IPW) was used to reduce any bias in treatment selection and other potential confounding factors. Results: Median follow-up time was 46.2 months. Before IPW, overall survival (OS) durations were significantly different among the 3 groups (median, 85 months for combined therapy, 56.5 months for chemoembolization alone, and 52.1 months for RF ablation alone; P = .01). The 10-year OS rates were 40.1%, 25.5%, and 19.5% for the combined, chemoembolization-only, and RF ablation-only groups, respectively. After IPW, OS remained superior in the combined chemoembolization/RF ablation group compared with the monotherapy groups (10-y OS, 41.8% with combined therapy, 28.4% with chemoembolization alone, and 11.9% with RF ablation alone; P = .022). Conclusions: Chemoembolization plus RF ablation may provide better survival outcomes than chemoembolization or RF ablation monotherapy, and can be considered a viable alternative treatment for unresectable single medium-sized HCCs.