Radioiodine-131 ((131)I) is widely used for diagnosis and treatment of benign thyroid diseases. Observational studies have not been conclusive about the carcinogenic potential of (131)I and we therefore conducted a meta-analysis. We performed a literature search till September 2011 which included (131)I as a diagnostic or treatment modality ((131)I for treatment of thyroid cancer was excluded). Data on 64 different organ or organ group subsets comprising 22 029 exposed subjects in the therapeutic cohorts and 24 799 in the diagnostic cohorts in seven studies were included. Outcome was pooled as the relative risk (RR) using both standard and bias adjusted methods. Quality assessment was performed using a study-specific instrument. No increase in overall (RR 1.06, 95% CI: 0.94-1.19), main organ group or combined organ group (four groups known to concentrate (131)I; RR 1.11, 95% CI: 0.94-1.31) risks was demonstrable. Individual organs demonstrated a higher risk for kidney (RR 1.70, 95% CI: 1.15-2.51) and thyroid (RR 1.99, 95% CI: 1.22-3.26) cancers with a strong trend for stomach cancer (RR 1.11, 95% CI: 0.92-1.33). A thyroid dose effect was seen for diagnostic doses. While there is no increase in the overall burden of cancer, an increase in risk to a few organs is seen which requires substantiation. The possible increase in thyroid cancer risk following diagnostic (131)I use should no longer be of concern given that it has effectively been replaced by the use of 99mTc-pertechnetate.