Introduction: Acutely painful osteoporotic vertebral compression fractures (OVCFs) are common in elderly individuals. Most OVCFs result from falls or routine activities, such as lifting objects or bending. OVCFs are associated with increased hospitalization, mortality and reduced quality of life. Calcitonin has been studied as an alternative or adjunct to opioid or non-opioid analgesia for treating acute pain associated with OVCFs. This review evaluates current evidence on the benefits and harms of calcitonin related to OVCFs. Methods: We registered our review protocol on PROSPERO (CRD42018084850) and conducted our study in compliance with PRISMA guidelines. We searched MEDLINE, EMBASE, The Cochrane Database of Systematic Reviews, clinical trials registries, conference papers and reference lists of included studies. Eligible studies evaluated the effect of calcitonin on pain scores in adults ≥60 years-old with a recent OVCF ( <45 days prior). Two reviewers independently screened studies, extracted data and allocated bias in duplicate. Data were pooled for meta-analysis using standard mean difference (SMD) and a random-effects model. Heterogeneity was evaluated with I2 and sensitivity analyses were performed. The certainty of evidence was assessed with GRADE criteria. Our primary outcome was pain; secondary outcomes include mobility and adverse events. Results: 1180 articles were screened, 11 eligible studies were identified and 9 (627 participants) were pooled for meta-analysis. Pain at rest was lower in the calcitonin group than the control group at week 1 (SMD -1.11, 95% confidence interval (CI) -1.95 to -0.26, I2 = 92%). Sensitivity analysis showed that the route of administration influenced this effect: the SMD for calcitonin nasal spray was -1.88 (95% CI -2.31 to -1.44, I2 = 53%) compared to -0.35 (95% CI -0.86 to 0.17, I2 = 60%) for intramuscular injection. Improvements in mobility were observed at week 4 (SMD -0.48, 95% CI -0.79 to -0.17, I2 = 45%). The risk of adverse events was increased with calcitonin (Risk Ratio 2.72, 95% CI 0.90 to 8.17, I2 = 41%) and consisted of flushing, headache, dizziness and gastrointestinal effects. The overall certainty of evidence was downgraded to low due to concerns over risk of bias and inconsistency between studies. Conclusion: Calcitonin, particularly as a nasal spray, is beneficial and safe for treating acute pain associated with OVCFs. Further studies are needed to improve the certainty of evidence.