<b><i>Objective:</i></b> Coma is the most serious disturbance of consciousness, which affects the life quality of patients and increases the burden of their family. Studies to assess the prognostic value of neuron-specific enolase (NSE) in patients with coma have not led to precise, generally accepted prognostic rules. The study aims to assess the correlation between NSE and prognosis of coma and the predictive value of NSE for clinical prognosis. <b><i>Methods:</i></b> A search was conducted using PubMed, Web of Science, EMBASE, Cochrane Library, China National Knowledge Infrastructure (CNKI), and WanFang Data from the establishment time of databases to December 2019. This analysis included patients with coma, regardless of how long the coma was. In total, 26 articles were retrieved and included in the review. <b><i>Results:</i></b> The meta-analysis revealed the NSE concentration of patients with coma is significantly higher than that of the control group (standard mean difference = 0.88, 95% confidence interval [CI]: 0.63–1.12, <i>p</i> < 0.05). The pooled sensitivity and specificity of NSE in coma diagnosis was 0.5 (95% CI: 0.39–0.61) and 0.86 (95% CI: 0.71–0.94). <b><i>Conclusions:</i></b> The NSE concentration of patients with poor coma prognosis is significantly higher than that of the control group. The high NSE concentration is not necessarily a poor prognosis for coma, but low NSE concentration indicates a high probability of a good prognosis for coma.