In this paper, we present results from a large number of experiments aimed at quantifying method and instrument uncertainty associated with laser diffraction analysis. We analyzed the size distribution of fine-grained sediment (< 1-50 μm) from Flathead Lake, Montana, along with samples from local fluvial, volcanic, and soil systems on a Malvern Mastersizer 2000 laser diffractometer. Our results indicate: (1) Optimal dispersion of fine-grained sediment was achieved by adding 5.5 g/l sodium hexametaphosphate for > 24 hours prior to analysis and using 60 seconds of ultrasonication during analysis. (2) Obscuration-a measure of the concentration of the suspension during analysis-produced the most reproducible results at about 20%. (3) Variations in refractive-index settings can significantly alter estimated grain-size distributions. (4) Assumed values for absorption (the degree to which sediment grains absorb the light) can have a profound effect on grain-size results. Absorption settings near 0 resulted in unexpected bimodal grain size distributions for sediments in the < 10 μm size fraction and significantly skewed the fine-grained tail of coarser samples, probably because of sub-optimal diffraction by particles with a diameter similar in size to the laser wavelength. Absorption settings closer to 1 produced very reproducible results and unimodal grain-size distributions over a wide range of refractive indexes. Our study has shown that laser diffraction can measure very fine-grained sediments (< 10 μm) quickly, with high precision (∼ 5% at 2 standard deviations), and without the need for extensive mineralogical determinations. These results make possible a new generation of studies in which high-resolution time-series data sets of sediment grain size can be used to infer subtle changes in paleohydrology.