Lubricants optimized for R-404A refrigerant may not be the best choice for the new low GWP alternatives. In this study, selected low GWP alternative refrigerants to R-404A are evaluated with several synthetic POE lubricants of systematically varied chemical structure and correspondingly varied compatibility with these refrigerants. The results of laboratory and full system tests are correlated to the measured thermo-physical properties and miscibility of the refrigerant/POE mixtures. Combining the property information with full system test data allow for analysis of the impact of refrigerant-lubricant mixture properties on system performance.