Image-enhanced endoscopy is helpful for screening of a second primary neoplasm in patients with esophageal and head and neck cancer. The purpose of this meta-analysis was to determine the diagnostic efficacy of white-light imaging (WLI), narrow band imaging (NBI), and Lugol chromoendoscopy for second primary neoplasm detection. A review of the PubMed/Cochrane databases up to May 2014 was performed. Meta-analysis was done by Meta-DiSc software and the Quality Assessment of Diagnostic Accuracy Studies-2 tool. A total of 4918 patients from 16 prospective and randomized trials were enrolled. For WLI, NBI, and Lugol chromoendoscopy, the pooled sensitivities were 53% (95% confidence interval [CI] = 48% to 59%), 87% (95% CI = 83% to 90%), and 88% (95% CI = 85% to 91%), respectively; the pooled specificities were 99% (95% CI = 98% to 99%), 95% (95% CI = 94% to 96%), and 63% (95% CI = 61% to 66%), respectively; and the areas under the receiver-operating characteristic (ROC) curve were 66%, 97%, and 82%, respectively. NBI endoscopy has the most highly accurate diagnostic performance for detection of second primary neoplasms in high-risk patients. © 2015 Wiley Periodicals, Inc. Head Neck 38: E2343-E2349, 2016.