Purpose To compare outcomes of radiation segmentectomy (RS) and segmental transarterial chemoembolization in treatment of unresectable, solitary hepatocellular carcinoma (HCC) ≤ 3 cm. Materials and Methods From January 2012 to January 2016, 534 and 877 patients were treated with radioembolization and transarterial chemoembolization, respectively. A cohort of 112 (radiation segmentectomy [RS], 55; chemoembolization, 57) locoregional therapy–naïve patients with solitary HCC ≤ 3 cm without vascular invasion or metastasis was retrospectively identified and stratified according to baseline patient demographics, tumor characteristics, and laboratory values. Propensity score matching (PSM) was conducted using a nearest neighbor algorithm (1:1). Outcomes analyzed included laboratory toxicities, imaging response, time to secondary therapy (TTST), and overall survival. Results Before PSM, complete response (CR) rate was 81.2% for RS and 49.1% for chemoembolization (odds ratio 2.2; 95% confidence interval [CI], 1.4–3.3; P <.001). Median (95% CI) TTST after initial therapy was 246 days (135–250 d) in chemoembolization group and 700 days (308–812 d) in RS group (hazard ratio 0.71; 95% CI, 0.55–0.92; P =.009). Overall survival before PSM was not significantly different between the 2 groups (P =.29). Overall CR rate after PSM was 92.1% in RS group and 52.6% in chemoembolization group (P =.005). Median (95% CI) TTST after matching was 161 days (76–350 d) in chemoembolization group and 812 days (363–812 d) in RS group (P =.001). Overall survival after matching was not significantly different between the 2 groups (P =.71). Conclusions RS results in improved imaging response and longer TTST compared with transarterial chemoembolization in treatment of early-stage HCC.