This study demonstrates how to use standardization and decomposition analysis (SDA) techniques to compare outcome measures simultaneously among multiple populations. Methamphetamine use among rural stimulant drug users in three geographically distinct areas of the US (Arkansas, Kentucky, and Ohio) is presented as an example of applying SDA. Findings show that the observed crude rate of ‘ever used’ methamphetamine in the past 30 days and the frequency of methamphetamine use in the past 30 days were much higher in Kentucky than in the other two states. However, after the compositions of socio-demographic confounding factors were standardized across the samples, the two measures of methamphetamine use ranked highest in Arkansas, followed by Kentucky, and then Ohio. Confounding factors contributed in various dimensions to the differences in the observed outcome measures among the distinct samples. The study shows that SDA is a useful technique for multi-population comparisons, providing an opportunity to look at data from a different perspective in medical studies.