Serum progesterone measurement has been advocated as a diagnostic tool in the non-invasive diagnosis of ectopic pregnancy. To assess the accuracy of a single serum progesterone measurement in the diagnosis of ectopic pregnancy, a meta-analysis was performed incorporating 26 studies evaluating the performance of single serum progesterone measurement in the diagnosis of ectopic pregnancy. A distinction was made in the diagnosis of pregnancy failure of any type versus viable intrauterine pregnancy and the diagnosis of ectopic pregnancy versus non-ectopic pregnancy. The reported sensitivity and specificity differed between the studies. Since there was a clear negative correlation between sensitivity and specificity, summary receiver-operating characteristic (ROC) curves could be estimated. The ROC curve for the diagnosis of pregnancy failure versus viable intrauterine pregnancy showed a good discriminative capacity. Single serum progesterone measurement could not discriminate between ectopic pregnancy and non-ectopic pregnancy. It is concluded that serum progesterone measurement can identify patients at risk for ectopic pregnancy, who need further evaluation, but its discriminative capacity is insufficient to diagnose ectopic pregnancy with certainty.