Objective: A Phase 3 randomized multicenter, double-blind, placebo-controlled trial (NCT02720692) compared once-daily intravenous (IV) meloxicam 30 mg to placebo, when added to the standard of care pain management regimens, in adults with moderate-tosevere pain following major elective surgery and concluded that meloxicam IV had a safety profile similar to placebo and reduced opioid consumption. Methods: In this post hoc subgroup analysis of orthopedic surgery subjects, 379 subjects received meloxicam IV 30 mg or IV-administered placebo every 24 hrs for ≤7 doses. Safety was assessed via AEs, laboratory tests, vital signs, and ECG, with an emphasis on specific AEs, including injection site reactions, bleeding, cardiovascular, hepatic, renal, thrombotic, and wound healing events. Daily opioid consumption was assessed during treatment. Results: Among meloxicam IV-treated subjects, 64.7% experienced ≥1 AE versus 68.8% of placebo-treated subjects. Investigators assessed most AEs to be mild or moderate in intensity and unrelated to treatment. Total opioid consumption (36.8 mg versus 50.3 mg IV morphine equivalent dose; P=0.0081) and opioid consumption during time points 0-24, 24-48, 0-48, and 0-72 hrs were statistically significantly lower in the meloxicam IV group. Conclusion: Meloxicam IV demonstrated no significant differences in the number and frequency of AEs versus placebo in subjects following orthopedic surgery. Opioid consumption was reduced in the meloxicam IV group versus placebo. Trial registration: ClinicalTrials.gov (Identifier: NCT02720692).