Objective: To evaluate whether measurement of maternal serum PP13 at 22 to 24 weeks of gestation, alone or in combination with second-trimester biochemical markers or uterine artery pulsatility measured by Doppler velocimetry, is useful in predicting those women at risk of developing pre-eclampsia. Study Design: A nested case-control study of pre-eclampsia cases with controls matched for gestational age and storage time for the maternal serum. PP13 was tested by an ELISA, with the samples blinded to pregnancy outcome. All patients also underwent uterine artery Doppler flow velocimetry at 22-24 weeks to measure the mean pulsatility index (PI). Results for Inhibin, Activin, PAPP-A and Free β-hCG were available from previous studies. Results: There were 73 controls and five cases with early pre-eclampsia in which delivery was induced prior to 35 weeks. In addition, there were a further seven cases with pre-eclampsia in which delivery was not induced before term. Median PP13 levels for controls and all cases were 295.9 and 212.6 pg/ml, and 171.2 pg/ml amongst the early pre-eclampsia cases, with the MoMs 1.00, 0.94 and 0.63, respectively (p < 0.001). Receiver operator characteristic (ROC) curve analysis for either all cases or early cases versus controls yielded areas under the curve of 0.588 (95% CI: 0.42-0.76; p = 0.1526) and 0.693 (0.47-0.92; p = 0.0441) for PP13. At a specificity set to 0.80, the sensitivity for PP13 in the early cases was 0.40 and that in all cases was 0.25. Combining PP13 bivariately with any of the markers (PI, PAPP-A, Activin, Inhibin or Free β-hCG) tested in the 22-24 week period did not improve the detection of early, late or all cases of pre-eclampsia compared with either marker alone. Conclusion: Late second-trimester PP13 alone is unlikely to be useful in predicting pre-eclampsia and early pre-eclampsia, and its prediction does not increase when coupled with second-trimester Doppler PI or other potential biochemical markers. Measuring between-trimester temporal changes may be worthy of further investigation.