BACKGROUND & AIMS: Colon capsule endoscopy (CCE) is a noninvasive technique used to explore the colon without sedation or air insufflation. A second-generation capsule was recently developed to improve accuracy of detection, and clinical use has expanded globally. We performed a systematic review and meta-analysis to assess the accuracy of CCE in detecting colorectal polyps. METHODS: We searched MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and other databases from 1966 through 2015 for studies that compared accuracy of colonoscopy with histologic evaluation with CCE. The risk of bias within each study was ascertained according to Quality Assessment of Diagnostic Accuracy in Systematic Reviews recommendations. Per-patient accuracy values were calculated for polyps, overall and for first-generation (CCE-1) and second-generation (CCE-2) capsules. We analyzed data by using forest plots, the I statistic to calculate heterogeneity, and meta-regression analyses. RESULTS: Fourteen studies provided data from 2420 patients (1128 for CCE-1 and 1292 for CCE-2). CCE-2 and CCE-1 detected polyps >6 mm with 86% sensitivity (95% confidence interval [CI], 82%-89%) and 58% sensitivity (95% CI, 44%-70%), respectively, and 88.1% specificity (95% CI, 74.2%-95.0%) and 85.7% specificity (95% CI, 80.2%-90.0%), respectively. CCE-2 and CCE-1 detected polyps >10 mm with 87% sensitivity (95% CI, 81%-91%) and 54% sensitivity (95% CI, 29%-77%), respectively, and 95.3% specificity (95% CI, 91.5%-97.5%) and 97.4% specificity (95% CI, 96.0%-98.3%), respectively. CCE-2 identified all 11 invasive cancers detected by colonoscopy. CONCLUSIONS: The sensitivity in detection of polyps >6 mm and >10 mm increased substantially between development of first-generation and second-generation colon capsules. High specificity values for detection of polyps by CCE-2 seem to be achievable with a 10-mm cutoff and in a screening setting.