Importance: The relationship between butter and plant-based oil intakes and mortality remains unclear, with conflicting results from previous studies. Long-term dietary assessments are needed to clarify these associations. Objective: To investigate associations of butter and plant-based oil intakes with risk of total and cause-specific mortality among US adults. Design, Setting, and Participants: This prospective population-based cohort study used data from 3 large cohorts: the Nurses' Health Study (1990-2023), the Nurses' Health Study II (1991-2023), and the Health Professionals Follow-up Study (1990-2023). Women and men who were free of cancer, cardiovascular disease (CVD), diabetes, or neurodegenerative disease at baseline were included. Exposures: Primary exposures included intakes of butter (butter added at the table and from cooking) and plant-based oil (safflower, soybean, corn, canola, and olive oil). Diet was assessed by validated semiquantitative food frequency questionnaires every 4 years. Main Outcomes and Measures: Total mortality was the primary outcome, and mortality due to cancer and CVD were secondary outcomes. Deaths were identified through the National Death Index and other sources. A physician classified the cause of death based on death certificates and medical records. Results: During up to 33 years of follow-up among 221 054 adults (mean [SD] age at baseline: 56.1 [7.1] years for Nurses' Health Study, 36.1 [4.7] years for Nurses' Health Study II, and 56.3 [9.3] years for Health Professionals Follow-up Study), 50 932 deaths were documented, with 12 241 due to cancer and 11 240 due to CVD. Participants were categorized into quartiles based on their butter or plant-based oil intake. After adjusting for potential confounders, the highest butter intake was associated with a 15% higher risk of total mortality compared to the lowest intake (hazard ratio [HR], 1.15; 95% CI, 1.08-1.22; P for trend < .001). In contrast, the highest intake of total plant-based oils compared to the lowest intake was associated with a 16% lower total mortality (HR, 0.84; 95% CI, 0.79-0.90; P for trend < .001). There was a statistically significant association between higher intakes of canola, soybean, and olive oils and lower total mortality, with HRs per 5-g/d increment of 0.85 (95% CI, 0.78-0.92), 0.94 (95% CI, 0.91-0.96), and 0.92 (95% CI, 0.91-0.94), respectively (all P for trend < .001). Every 10-g/d increment in plant-based oils intake was associated with an 11% lower risk of cancer mortality (HR, 0.89; 95% CI, 0.85-0.94; P for trend < .001) and a 6% lower risk of CVD mortality (HR, 0.94; 95% CI, 0.89-0.99; P for trend = .03), whereas a higher intake of butter was associated with higher cancer mortality (HR, 1.12; 95% CI, 1.04-1.20; P for trend < .001). Substituting 10-g/d intake of total butter with an equivalent amount of total plant-based oils was associated with an estimated 17% reduction in total mortality (HR, 0.83; 95% CI, 0.79-0.86; P < .001) and a 17% reduction in cancer mortality (HR, 0.83; 95% CI, 0.76-0.90; P < .001). Conclusions and Relevance: In this cohort study, higher intake of butter was associated with increased mortality, while higher plant-based oils intake was associated with lower mortality. Substituting butter with plant-based oils may confer substantial benefits for preventing premature deaths.