The EINSTEIN-PE trial investigators evaluated the efficacy and safety of oral rivaroxaban alone versus standard therapy (enoxaparin followed by a vitamin K antagonist) in patients with acute symptomatic pulmonary embolism. The study included 4832 patients and used a noninferiority design to compare the two treatments. The primary efficacy outcome was symptomatic recurrent venous thromboembolism, and the principal safety outcome was major or clinically relevant nonmajor bleeding. Rivaroxaban was found to be noninferior to standard therapy for the primary efficacy outcome (hazard ratio, 1.12; 95% CI, 0.75 to 1.68; P=0.003) but had a similar rate of the principal safety outcome (hazard ratio, 0.90; 95% CI, 0.76 to 1.07; P=0.23). Major bleeding occurred in 1.1% of patients in the rivaroxaban group and 2.2% in the standard-therapy group (hazard ratio, 0.49; 95% CI, 0.31 to 0.79; P=0.003). The findings suggest that a fixed-dose regimen of rivaroxaban alone is noninferior to standard therapy for the initial and long-term treatment of pulmonary embolism and may offer a potentially improved benefit-risk profile.The EINSTEIN-PE trial investigators evaluated the efficacy and safety of oral rivaroxaban alone versus standard therapy (enoxaparin followed by a vitamin K antagonist) in patients with acute symptomatic pulmonary embolism. The study included 4832 patients and used a noninferiority design to compare the two treatments. The primary efficacy outcome was symptomatic recurrent venous thromboembolism, and the principal safety outcome was major or clinically relevant nonmajor bleeding. Rivaroxaban was found to be noninferior to standard therapy for the primary efficacy outcome (hazard ratio, 1.12; 95% CI, 0.75 to 1.68; P=0.003) but had a similar rate of the principal safety outcome (hazard ratio, 0.90; 95% CI, 0.76 to 1.07; P=0.23). Major bleeding occurred in 1.1% of patients in the rivaroxaban group and 2.2% in the standard-therapy group (hazard ratio, 0.49; 95% CI, 0.31 to 0.79; P=0.003). The findings suggest that a fixed-dose regimen of rivaroxaban alone is noninferior to standard therapy for the initial and long-term treatment of pulmonary embolism and may offer a potentially improved benefit-risk profile.