Background: Changes over time in preferences for life-sustaining treatments (LSTs) at end of life (EOL) in different patient cohorts are not well established, nor is the concept that LST preferences represent more than 2 groups (uniformly prefer/not prefer). Purpose: The purpose of this study was to explore heterogeneity and changes in patterns of LST preferences among 2 independent cohorts of terminally ill patients with cancer recruited a decade apart. Methods: Preferences for cardiopulmonary resuscitation, intensive care unit care, cardiac massage, intubation with mechanical ventilation, intravenous nutritional support, nasogastric tube feeding, and dialysis were surveyed among 2,187 and 2,166 patients in 2003–2004 and 2011–2012, respectively. Patterns and changes in LST preferences were examined by multigroup latent class analysis. Results: We identified 7 preference classes: uniformly preferring, uniformly rejecting, uniformly uncertain, favoring nutritional support but rejecting other treatments, favoring nutritional support but uncertain about other treatments, favoring intravenous nutritional support with mixed rejection of or uncertainty about other treatments, and preferring LSTs except intubation with mechanical ventilation. Probability of class membership decreased significantly over time for the uniformly preferring class (15.26%–8.71%); remained largely unchanged for the classes of uniformly rejecting (41.71%–40.54%) and uniformly uncertain (9.10%–10.47%), and favoring nutritional support but rejecting (20.68%–21.91%) or uncertain about (7.02%–5.47%) other treatments, and increased significantly for the other 2 classes. The LST preferences of Taiwanese terminally ill patients with cancer are not a homogeneous construct and shifted toward less-aggressive treatments over the past decade. Conclusions: Identifying LST preference patterns and tailoring interventions to the unique needs of patients in each LST preference class may lead to the provision of less-aggressive EOL care.