Background Preventing acute postsurgical pain (PSP) following breast cancer surgery is a major issue. Thoracic paravertebral block (TPVB) has been widely studied for this indication. Erector spinae plane block (ESPB) has been assumed to be effective. We aimed to compare the efficacy and safety of ESPB over TPVB in preventing acute PSP. Methods In this prospective observational study, 120 patients admitted for unilateral major oncologic breast surgery received T2/T3 ESPB (ropivacaine 0.75%, 0.35 ml.kg -1 ), and 102 were analysed. Then, the ESPB cohort was compared to a TPVB cohort from the experimental arm of a randomized controlled study with the same protocol (NCT02408393) using propensity score matching analysis. The primary outcome was the need for morphine consumption in the PACU. Secondary outcomes were the morphine total dose, the incidence of ESPB and TPVB complications, and discontinuous visual analogue scale measurement trends at rest and at mobilization in the 24 hours after surgery. Results A total of 102 patients completed the study between December 2018 and August 2019. Propensity score matching formed 94 matched pairs. The proportion of morphine titration in the PACU was higher in the ESPB group than in the TPVB group (74.5% vs. 41.5%, p<0.001), with a between-group difference of 33.0% (95% CI [19.3%, 46.7%]). No ESPB-related complications were observed. Conclusion ESPB is less effective in preventing morphine consumption in the PACU than TPVB. Our findings do not support the use of ESPB as the first-line regional anaesthesia for major breast cancer surgery. Randomized trials comparing ESPB and TPVB are needed.