Summary: Given a predictor of outcome derived from a high-dimensional dataset, pre-validation is a useful technique for comparing it to competing predictors on the same dataset. For microarray data, it allows one to compare a newly derived predictor for disease outcome to standard clinical predictors on the same dataset. We study pre-validation analytically to determine if the inferences drawn from it are valid. We show that while pre-validation generally works well, the straightforward “one degree of freedom” analytical test from pre-validation can be biased and we propose a permutation test to remedy this problem. In simulation studies, we show that the permutation test has the nominal level and achieves roughly the same power as the analytical test.