Purpose: To evaluate the efficacy and safety of transarterial chemoembolization with polyethylene glycol (PEG) drug-eluting embolic agents in the treatment of hepatocellular carcinoma (HCC). Materials and Methods: A single-center retrospective study of 302 patients (258 men; 85.4%) with HCC treated during a 20-month period was conducted. The mean patient age was 66 years ± 10; 142 (47%) had Barcelona Clinic Liver Cancer stage A disease and 134 had (44.4%) stage B disease; 174 (57.6%) had a single HCC tumor, 65 (21.5%) had 2, and 62 (20.9%) had 3 or more. Mean index tumor size was 36.6 mm ± 24.8. One-month follow-up computed tomography (CT) response per modified Response Evaluation Criteria In Solid Tumors and clinical and biochemical safety were analyzed. Progression-free and overall survival were calculated by Kaplan–Meier method. Results: Median follow-up time was 11.9 months (95% confidence interval, 11.0–13.0 mo). One-month follow-up CT revealed complete response in 179 patients (63.2%), partial response in 63 (22.3%), stable disease in 16 (5.7%), and progressive disease in 25 (8.8%). The most frequent complications were postembolization syndrome in 18 patients (6%), liver abscess in 5 (1.7%), and puncture-site hematoma in 3 (1%). Biochemical toxicities occurred in 57 patients (11.6%). Survival analysis at 12 months showed a progression-free survival rate of 65.9% and overall survival rate of 93.5%. Patients who received transplants showed a 57.7% rate of complete pathologic response. Conclusions: Chemoembolization with PEG embolic agents for HCC is safe and effective, achieving an objective response rate of 85.5%.