Background: Radical mastectomy often causes acute and chronic pain. One aimed to explore whether unilateral, ultrasound-guided, single-injection modified intercostal nerve block (MINB) could improve postoperative analgesia compared with no-MINB (Control group) in patients undergoing radical mastectomy. Methods: Sixty-five patients were randomly assigned to receive no-MINB (Control group) or MINB (MINB group) with 0.33 % ropivacaine (30 ml). The primary outcome was Visual Analogue Scale (VAS) scores at rest 6 h postoperatively. Secondary outcomes included VAS scores at rest and during movement at 0 h, 12h, 24h, 48h, and 90 days postoperatively; use of intraoperative opioids; postoperative rescue analgesia; time of first ambulation; complications; and score of China version of the Quality of recovery-15 (QoR-15) questionnaire (0 = extremely poor QoR; 150 = excellent QoR) at 24 h after surgery. Results: The MINB group showed lower resting VAS (resting) pain score at 6 h postoperatively (median [interquartile], 1 (0–2), vs 2 (2–3), 95 % CI difference in medians 1–2; P