Chronic postsurgical pain is a challenging problem after breast cancer surgery. This prospective, randomized, double-blinded, parallel-group, placebo-controlled trial was conducted to evaluate the influence of preoperative ultrasound-guided multilevel paravertebral blocks (PVBs) on chronic pain following mastectomy.One hundred eighty-four women were randomized to receive ultrasound-guided multilevel (T1-T5) PVBs with 5 mL of ropivacaine 0.5% or normal saline per level. The primary end point was the incidence of chronic pain at 3 months following mastectomy assessed by the brief pain inventory (BPI), while the secondary end points were the acute postoperative pain, the number of patients requiring rescue analgesia, postoperative nausea and vomiting (PONV), side effects, and chronic pain at 6 months after surgery assessed by the BPI.A total of 172 patients completed the study. Ultrasound-guided multilevel PVBs significantly decreased immediate postoperative pain for the first 12 hours (<0.001). Additionally, fewer patients in the PVB group required rescue analgesia in the first 48 hours post-operatively compared to the control group (5/86 vs 28/86, OR =0.128, 95% CI: 0.047-0.351, <0.001). No statistically significant difference was tested between the two groups (9.3% vs 17.4%, OR =0.419, 95% CI: 0.162-1.087, =0.068) in the incidence of PONV. At 3 months, the incidence of chronic pain (BPI average pain score ≥3) was 34.5% and 51.2% (OR =0.511, 95% CI: 0.277-0.944, =0.031) in the PVB and control groups, respectively, and at 6 months, the incidence was 22.1% and 37.2% (OR =0.479, 95% CI: 0.245-0.936, =0.03), respectively. No complications occurred during the study.This study indicated that perioperative ultrasound-guided multilevel PVBs with ropivacaine improved acute postoperative pain and decreased postmastectomy chronic pain at 3 and 6 months postoperatively.