To compare radiofrequency (RF) ablation with nonanatomic resection (NAR) as first-line treatment in patients with a single Barcelona Clinic Liver Cancer (BCLC) stage 0 or A hepatocellular carcinoma (HCC) and to evaluate the long-term outcomes of both therapies. This retrospective study was approved by the institutional review board. The requirement for informed consent was waived. Data were reviewed from 580 patients with HCCs measuring 3 cm or smaller (BCLC stage 0 or A) who underwent ultrasonographically (US) guided percutaneous RF ablation (n = 438) or NAR (n = 142) as a first-line treatment. Local tumor progression, intrahepatic distant recurrence, disease-free survival, and overall survival rates were analyzed by using propensity score matching to compare therapeutic efficacy. In addition, major complications and length of postoperative hospital stay were compared. Before propensity score matching (n = 580), the 5-year cumulative rates of local tumor progression for RF ablation and NAR (20.9% vs 12.7%, respectively; P = .093) and overall survival rates (85.5% vs 90.9%, respectively; P = .194) were comparable, while the 5-year cumulative intrahepatic distant recurrence rates (62.7% vs 36.6%, respectively; P < .001) and disease-free survival rates (31.7% vs 61.1%, respectively; P < .001) in the NAR group were significantly better than those in the RF ablation group. After matching (n = 198), there were no significant differences in therapeutic outcomes between the RF ablation and NAR groups, including 5-year cumulative intrahepatic distant recurrence (47.0% vs 40.2%, respectively; P = .240) and disease-free survival rates (48.9% vs 54.4%, respectively; P = .201). RF ablation was superior to NAR for major complication rates and length of postoperative hospital stay (P < .001). In patients with one BCLC stage 0 or A (≤ 3 cm) HCC who received RF ablation or NAR as first-line treatment, there were no significant differences in long-term therapeutic outcomes; however, RF ablation was associated with fewer major complications and a shorter hospital stay after treatment.