OBJECTIVE: Osteoarthritis (OA) is the most common joint disease and leading cause of pain and disability in the elderly population. Most guidelines recommend the use of non-steroidal anti-inflammatory drugs (NSAIDs) and opioids for the non-operative treatment of OA. Monoclonal nerve growth factor (NGF) antibodies are new drugs with the potential to provide pain relief and functional improvement in OA. We compared the efficacy (pain reduction and functional improvement), and safety of monoclonal NGF antibodies with NSAIDs and opioids in the treatment of OA with a Bayesian network meta-analysis. RESULTS: 38 articles, comprising 41 trials and 20489 patients with OA were included. Overall from the network meta-analysis, anti-NGFs were the most effective drugs for pain relief (Standardized Mean Difference or SMD compared with placebo 4.25, 95% CI 2.87 to 5.63, Surface Under the Cumulative RAnking curve or SUCRA=93.7%) and for functional improvement (SMD 4.90, 95% CI 3.46 to 6.33, SUCRA=98.3%). Although anti-NGFs were associated with higher risk of peripheral sensation abnormality (paresthesia and pruritus), they were not associated with higher risk of other AEs (headaches and nausea) or with higher withdrawal rates related to AEs. CONCLUSIONS: Monoclonal NGF antibodies provide significantly greater pain relief and functional improvement in OA compared to NSAIDs and opioids. Monoclonal NGF antibodies are not associated with severe AEs. More studies are needed to confirm these findings. METHODS: PubMed, CNKI, Web of Science, Scopus, Embase and Cochrane Library databases were searched for relevant studies (OA treated with anti-NGFs, opioids, selective COX-2 inhibitors or NSAIDs) published between January 1999 to January 2020. Bayesian network and conventional meta-analyses were conducted. Pain relief, functional improvement and AEs were assessed.