Six randomized controlled trials including a total of 1254 patients with acute musculoskeletal injuries were included in this meta-analysis comparing oral paracetamol to oral combination therapy. The primary outcome of interest was pain at rest, which was assessed at 2, 24, and 72 hours follow-up. Secondary outcomes of interest included pain during movement evaluated at 2, 24, and 72 hours follow-up, the need for additional analgesia measured at 2 hours and 1 week, and incidence of adverse events. Pooled outcomes for pain at rest and during movement at all timepoints were not statistically significantly different between the paracetamol and combination group (p>0.05 for all). Pooled results for the requirement of additional analgesia at 2 hours was statistically significantly favored in the paracetamol group compared to the combination group (p=0.01) but this trend was not observed at 1 week follow-up (p=0.59). For the incidence of adverse events, heterogeneity was high; thus, subgroup analyses were conducted. For the incidence of adverse events when analyzing paracetamol combination with an NSAID at 2 hours and 1 week follow-up, no statistical significant difference were observed (p=0.76; p=0.32, respectively). For the subgroup analysis of concomitant Omeprazole, the incidence of adverse events pooled results were favored in the combination group (p=0.01) while for the subgroup of combination with NSAID and opioid analgesics, the pooled results were favored in the paracetamol group (p=0.007).