In this multicenter retrospective study, we aimed to analyze the dose-response and survival relationships and estimate the tumor absorbed radiation dose required to achieve response in colorectal cancer liver metastases treated with 90Y glass microspheres. Methods: Patients with metastatic colorectal cancer treated with 90Y glass microspheres were included in this retrospective study. Mean perfused volume, mean estimated perfused volume absorbed dose, mean estimated tumor absorbed dose (ETAD), mean estimated perfused normal liver absorbed dose, and mean estimated whole liver absorbed dose were calculated using [99mTc]-macroaggregated albumin SPECT images. Treatment to response was evaluated by [18F]-FDG PET images. Results: In total, 176 patients (112 men and 64 women) were included in the analysis. A strong correlation was found between mean ETAD and response to treatment (P = 0.001). The cutoff values to predict a response were calculated as 109 Gy (sensitivity, 68%; specificity, 73%; area under the curve, 0.728; P = 0.001) for mean estimated perfused volume absorbed dose and 152 Gy (sensitivity, 93%; specificity, 89%; area under the curve, 0.945; P = 0.001) for mean ETAD. The median overall survival (OS) of patients with a mean ETAD higher than 152 Gy was significantly longer than that of the remaining patients, at 18.1 mo (95% CI, 15.7-20.4 mo) versus 12.8 mo (95% CI, 10.6-15.0 mo; P = 0.030). Further analysis using maximally selected rank statistics to better predict OS showed that patients with a minimum mean ETAD of 203 Gy had OS 6.4 mo longer than the OS of those with a lower mean ETAD (P = 0.022). Conclusion: A mean radiation dose to the tumor of at least 152 Gy may predict a metabolic response. Although a threshold of 152 Gy predicted longer OS, a mean ETAD of 203 Gy, when achievable, predicted even longer OS than found for those with a mean ETAD of less than 203 Gy.