Objective: To investigate the frequency of split hand (SI) and its diagnostic performance in amyotrophic lateral sclerosis (ALS). Methods: PubMed, EMBASE, OVID and other databases were searched systematically up to March 2021 for relevant reports about the split hand syndrome. Two reviewers screened and selected the titles and abstracts of the studies independently during the database searches and performed full-text reviews and extracted available data. In our study, AACMAP was calculated by AACMAP = APBCMAP/ADMCMAP and split-hand index (SI) was calculated by SICMAP = (APBCMAP x FDICMAP)/ADMCMAP. The mean differences (MD) in APB/ADMCMAP and SICMAP between patients with ALS and control group were calculated (APB the abductor pollicis brevis muscle; ADM the abductor digiti minimi muscle; CMAP compound muscle action potentials). Meta-analysis was performed to determine summary sensitivity, specificity, and area under the curve (AUC) with 95% confidence intervals (CI) for SICMAP. Results: Pooled results of five studies including 339 patients showed that 50% (95%CI: 35%-65%) of patients with ALS presented split hand. APB/ADMCMAP in patients with ALS was significantly lower than healthy population (MD: -0.38, 95%CI: -0.48, -0.28). SICMAP in patients with ALS was significantly lower than healthy controls (MD: -5.87, 95%CI: -6.28, -5.46) and neuromuscular controls (MD: -5.60, 95%CI: -5.78, -5.42). Receiver operating characteristic curve analysis showed that the AUC was 0.860 [95%CI: 0.808, 0.911] for SICMAP. The sensitivity and specificity for SICMAP were 78% and 81% (cut-off value: 5.2- 11.8), respectively. Conclusion: Half of ALS patients might show split hand sign. SICMAP could be a potential biomarker in the diagnosis of ALS.