Prior studies demonstrated that secondary acute promyelocytic leukemia (sAPL) and de novo APL may but not consistently have similar overall survival (OS). We used the Surveillance, Epidemiology, and End Results (SEER) 13 database to compare their OS. Patients with sAPL (n = 90), compared to de novo APL (n = 1600), were more likely to be older, White and diagnosed after year 2005. Mortality rate at 1 month (28.9% vs. 23.0%, p = 0.20) and 5-year OS (42% vs. 50%, p = 0.24) was similar between sAPL and de novo APL. In a multivariate analysis, sAPL was associated with similar OS as de novo APL (hazard ratio, HR 1.11; 95% confidence interval, CI 0.78-1.58; p = 0.546). This population-based study demonstrated no difference in OS or early mortality rate between sAPL and de novo APL. sAPL can be managed very similarly to de novo APL and does not need to be excluded from clinical trials of APL.