STUDY OBJECTIVE: The study objective is to identify differences in postoperative pain management according to different analgesic treatments, targeting 2 main pathways involved in pain perception. DESIGN: The design is a randomized, parallel groups, open-label study. SETTING: The setting is in an operating room, postoperative recovery area, and surgical ward. PATIENTS: There are 200 patients undergoing open inguinal hernia repair (IHR) with tension-free technique (mesh repair). INTERVENTIONS: The intervention is a randomization to receive ketorolac (group K) or tramadol (group T) for 3 days after surgery. MEASUREMENTS: The measurements are differences in analgesic efficacy (numeric rating scale [NRS]) in the postoperative (up to 5 days) period, chronic pain incidence (1 and 3 months), side effects, and complications. MAIN RESULTS: We found no differences in analgesic efficacy (NRS value ≥4 in the first 96 hours: 26% in group K vs 32% in group T, P = .43); the proportion of patients with NRS ≥4 was similar in both groups, and the time trajectories were not significantly different (P for interaction = .24). Side effects were higher (12% vs 6%) in the tramadol group, although not significantly (P = .14), with a case of bleeding in the ketorolac group and higher incidence of constipation in tramadol group. One patient in each group developed chronic pain. CONCLUSIONS: Ketorolac or weak opioids are equally effective on acute pain and on persistent postsurgical pain development after IHR, and drug choice should be based on their potential side effects and patient's comorbidities. Further studies are needed to standardize the most rational approach to prevent persistent postsurgical pain after IHR. TRIAL REGISTRATION: ClinicalTrials.gov NCT01345162.