Cisplatin and nedaplatin show significant antitumor activity and have been widely used for esophageal squamous cell carcinoma (ESCC). However, it is still unclear whether the efficacy and safety of nedaplatin-based regimens are comparable to those of cisplatin-based regimens in patients with metastatic/recurrent or advanced ESCC. Therefore, we conducted a systematic review and meta-analysis to compare the efficacy and safety of these two regimens for the treatment of metastatic/recurrent and advanced ESCC. We systematically searched Pubmed, Web of Science, and the Cochrane Database, as well as abstracts presented at conferences (all up to January 2015), for randomized-controlled and nonrandomized clinical trials that compared cisplatin-based and nedaplatin-based regimens in patients with metastatic/recurrent or advanced ESCC. Data were extracted from the original studies by two independent reviewers. This meta-analysis was performed usingReviewManager (RevMan) Version 5.3 (Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, 2014) software. Ten eligible trials, including 598 patients diagnosed with metastatic/recurrent or advanced ESCC, were included in our analysis. Our results demonstrated that the nedaplatin-based regimens were comparable to the cisplatin-based regimens in terms of overall survival (OS) (hazard ratio, HR: 1.22, 95% confidence interval, CI: 0.86-1.74, p=0.26) and overall response rate (ORR) (risk ratio, RR: 0.92, 95% CI: 0.77-1.10, p=0.37) and generated fewer grade 3 and 4 side effects including nausea (RR: 3.41, 95% CI: 1.67-6.96, p<0.001) and vomiting (RR: 3.62, 95% CI: 1.77-7.40, p<0.001) and fewer grade 1 and 2 adverse events including nausea (RR: 1.54, 95% CI: 1.23-1.93, p<0.001), vomiting (RR: 1.76, 95% CI: 1.76-2.30, p<0.001), peripheral neuropathy (RR: 1.75, 95% CI: 1.08-2.84, p=0.02) and renal dysfunction (creatinine) (RR: 3.28, 95% CI: 1.37-7.84, p=0.008). This systematic review and meta-analysis indicated that the efficacy of nedaplatin-based regimens was comparable to that of cisplatin-based regimens for patients with metastatic/recurrent or advanced ESCC, and that nedaplatin-based regimens were associated with less toxicity and better tolerability. However, this study was a meta-analysis of previously released data; therefore, there is a potential publication bias and heterogeneity among the included trials. Future, well-designed RCTs with large cohorts are warranted.