Background: Osteosarcoma is the most common primary bone sarcoma. Currently, the main treatment option for high-grade osteosarcomas is neoadjuvant chemotherapy, followed by surgical resection of the lesion and adjuvant chemotherapy. Limb salvage surgery (LSS) and amputation are the main surgical techniques; however, controversy still exists concerning the best surgical method. Our meta-analysis compared the effectiveness of LSS and amputation combined with neoadjuvant chemotherapy in patients with limb osteosarcoma, in terms of 5-year overall survival (OS), 5-year disease-free survival (DFS) and local recurrence rate.Methods: Following the established methodology of PRISMA guidelines, a literature search was conducted in PubMed, Cochrane, Google Scholar from 1975 until January 2020. Two independent reviewers evaluated the study quality based on the Newcastle-Ottawa scale. Odds ratio and 95% confidence interval of the OS, DFS and local recurrence rate were calculated.Results: Thirteen studies were finally included with a total of 2884 patients; 1986 patients undergone LSS and 898 amputations. Five-year overall survival was almost 2-fold in patients treated with LSS than those treated with amputation (OR: 1.99; 95% CI: 1.35-2.93; I = 74%, p < 0.001). No difference was found in 5-year DFS between LSS patients and amputees (OR: 1.24; 95% CI: 0.55-2.79; I = 67%, p = 0.01). The odds of local recurrence was numerically higher in LSS compared to amputation but not statistically significant (OR: 2.29; 95% CI: 0.95-5.53; I = 47%, p = 0.05). However, the included studies did not clearly define differences in the stages of patients of the two groups.Conclusion: Our study demonstrated that in patients with limb osteosarcoma treated with neoadjuvant chemotherapy, LSS is associated with a higher 5-year overall survival and the odds of local recurrence may be increased but these results should be interpreted with caution due to high heterogeneity.