In this study, gauge repeatability and reproducibility (gauge R&R) was used to analyze variability for USP apparatus 2 dissolution measurement systems. Experiments were designed to assess the variability due to apparatus, operator, and sample tablet. Since dissolution testing is a destructive test, a nested model was used for data analysis. Additionally, perturbation tests with both disintegrating and nondisintegrating tablets were performed to study the variability due to sample position within the dissolution vessel. For the gauge R&R study, two well-trained chemists used two mechanically calibrated USP apparatus 2 units. Six tests were performed by each operator on each apparatus. Evaluation of dissolution test results at 30 min using an internal DPA calibrator tablet NCDA#2 (10 mg prednisone) indicates that the main contribution to the total variance, approximately 70%, is due to the sample tablets, approximately 25% is from the apparatus and approximately 5% is due to the operators. There is no significant difference between operators and apparatuses as shown by the gauge R&R studies. In addition, dissolution results can be strongly affected by the position of the tablet within the vessel. Similarity (f 1 ) and dissimilarity (f 2 ) factors were calculated to statistically evaluate differences between perturbed and normal dissolution tests.