Studies designed to assess persistent postoperative pain (PPP) incidence after hepatectomies are lacking. Our aim was to assess PPP incidence 6 months after hepatectomies with intravenous (IV) or epidural (EPI) analgesia containing ketamine. Prospective observational comparative study between 2 cohorts of patients submitted to hepatectomy. Patients received 1 of 2 analgesic regimes containing ketamine: EPI group or IV group. Visual analog scale (VAS), Neuropathic Pain Symptom Inventory (NPSI), Pain Catastrophizing Scale (PCS), and quantitative sensorial testing (QST: to determine area of hyperalgesia/allodynia) were assessed preoperatively and postoperatively at 2 h, 24 h, 7 days, 1 month, and 6 months. VAS ≥ 1 at 1 and 6 months was considered indicative of PPP and VAS > 3 was considered as not controlled pain. Side effects and complications were registered. Forty-four patients were included: 23 in EPI group and 21 in IV group. Patients in IV group were older and had more comorbidities. No patient presented VAS > 3 at 1 or 6 months. VAS ≥ 1 at 1 and 6 months was 36.4% and 22.7%, respectively. No differences in VAS, NPSI, or PCS were found between groups. Allodynia/hyperalgesia area did not differ between groups and was infrequent and slight. Pain pressure threshold in the wound vertical component was significantly higher in EPI group after 7 days. IV group showed more cognitive side effects. Incidence of PPP at 6 months after open hepatectomies with EPI or IV analgesia containing ketamine was lower than previously reported for other abdominal surgeries. Ketamine influence on low PPP incidence and hyperalgesia cannot be discarded.