Background: Outcomes of acute promyelocytic leukemia (APL) have significantly improved with the availability of targeted agents. It remains unclear whether the population-level outcomes of APL have improved over time. Methods: Using the SEER database, we identified patients aged ≥20 years with pathologically confirmed APL diagnosed in 2000 through 2014 and who were actively followed. Patients were stratified by diagnosis period into 3 groups (2000–2004, 2005–2009, and 2010–2014) to assess the temporal trends in overall survival (OS), cause-specific survival (CSS), and other outcomes. Results: A total of 2,962 patients with a median age of 48 years (range, 20–96 years) were included. Hispanic patients constituted 21.5% of the cohort and the largest proportion (47.9%) of uninsured patients. The incidence of APL was 0.33 cases per 100,000 population per year. Incidence varied significantly by age, sex, race/ethnicity, and diagnosis period. Survival was significantly higher for patients diagnosed in 2010 through 2014 compared with those diagnosed in 2005 through 2009 and in 2000 through 2004 (4-year OS, 73.4% vs 65.6% vs 57.3%, respectively; 4-year CSS, 78.3% vs 70.8% vs 60.8%, respectively). Early mortality improved significantly over time (2000–2004, 25.3%; 2005–2009, 20.6%; 2010–2014, 17.1%) and was higher in men and Hispanic patients. According to multivariate analysis, diagnosis before 2010 and unmarried status were associated with a higher mortality risk. Uninsured patients had a significantly higher early mortality without a significant difference in post-30-day CSS. No significant changes were noted in risk of secondary malignancies. Conclusions: Population-level outcomes of APL have continued to improve over time. However, significant discrepancies in disease outcomes continue to exist, highlighting the need for more research.