To explore the feasibility, effectiveness, and safety of ultrasound-guided intercostal nerve block (ICNB) for immediate relief of moderate and severe pain following esophagectomy in a postanesthesia care unit (PACU). Eighty-one patients who complained of moderate to severe pain on arrival to the PACU after an Ivor Lewis esophagectomy were randomly assigned to 2 groups: a sufentanil treatment group (Group A, n = 41) and an intercostal nerve block treatment group (Group B, n = 40). The visual analog scale (VAS) pain scores at rest and on cough at 1, 2, 4, 12, 24, and 48 hours after treatment were monitored. The heart rate, blood pressure, and pulse oxygen saturation (SpO2 ) 2 hours after treatment and the patients' length of stay in the PACU after treatment were recorded. Patient-controlled intravenous analgesia consumption and the incidence of nausea, vomiting, and other adverse reactions were also recorded. Ultrasound-guided ICNB was performed successfully in all patients in Group B without puncture-related complications. The VAS pain scores at rest and on cough at 1, 2, and 4 hours after treatment in Group B were significantly lower than those in Group A (P < 0.05). The consumption of sufentanil and the incidence of nausea and vomiting were significantly decreased in Group B compared with those in Group A. Ultrasound-guided ICNB could provide effective and safe pain relief for patients who suffer from moderate to severe pain (VAS score ≥ 5) after esophagectomy in the PACU. © 2018 World Institute of Pain.