We report the results of a study of hydrogen isotope analysis of silicate glasses by secondary ion mass spectrometry (SIMS) using a Cameca 6F ion probe. Large differences between measured and true D/H ratios result from instrumental mass fractionation (IMF); the measured D/H ratios are depleted in the heavy isotope by an average of − 220‰ but with a total range of 60‰. Differences in IMF within subsets of glasses correlate with variables such as H2O abundance, density, and other chemical parameters and these variations constitute a significant matrix effect. The energy- and composition-dependence of hydrogen isotope IMF in glasses is well described by kinetic energy transfer analysis in a simple elastic two-collision cascade model, and provides important insight into the origins of matrix effects in SIMS. The analysis leads to a correction method for D/H matrix effects that predicts the measured IMF values to within ± 8‰, and an example data reduction is given for analysis of submarine glasses from the Reykjanes Ridge.