Purpose: The present study aimed at assessing the efficiency of ropivacaine on post-operative pain for extraction of third molars.Methods: In a single centre, prospective, parallel, double blind randomised trial, patients scheduled for removal of all four third molars, ASA I-III patients<65 year-old patients were included. After intubation under general anesthesia (using intravenous remifentanil and propofol), for each of the third molars, 2mL of ropivacaine (7.5mg/mL) or placebo (0.9% saline solution) was injected into the vestibular capsule (total: 8mL) before extraction. At the end of surgery, similar analgesia was injected for both groups (intravenous paracetamol 1g and ketoprofene 100mg). The primary outcome was postoperative pain assessed by Visual Analog Scale (VAS). Postoperative consumption of analgesics (morphine titration in post-operative care unit when VAS>3/10, followed by oral tramadol 50mg after discharge), patient satisfaction, chronic pain (1-3 month), time in PACU and total hospitalization time were also recorded.Results: A total of 50 patients were analysed in each group with similar characteristics (ropivacaine vs. control, for age (years) 18 [17-21] vs. 18 [17-21], for sex (female) 33 (66%) vs. 25 (50%), and BMI (kg/m2): 20 [19-23] vs. 21 [19-23]). Area Under the Curve for VAS pain (0 to 4h) was lower for Ropivacaine group: 0.43 [0.19-0.66] vs. 0.63 [0.43-0.87], P=0.005. Use of morphine in PACU (8 vs. 18, P=0.02) and median length of stay in ambulatory setting (5 vs. 6h, P=0.03) were reduced in Ropivacaine vs. Placebo group. At days 1 and 4, VAS of pain was higher in Ropivacaine group (respectively 4 vs. 2, P=0.006 and 3 vs. 2, P=0.05). At month 1 and 3, pain and DN4 score were similar between groups, with a median VAS pain score at 0 for both groups (P=0.42). No difference was observed for patient satisfaction and adverse events.Conclusions: Ropivacaine provides an immediate efficient pain relief after extraction of third molars without benefit after discharge.Clinicaltrial registration: NCT01541059.