In Reply We greatly appreciate the acknowledgment of our analysis on sex differences in the TWILIGHT trial1 in a Letter to the Editor by Chen and colleagues. The authors of the letter point out to our statement that in the TWILIGHT trial, the incremental bleeding risk associated with female sex was no longer significant after adjustment for baseline characteristics, suggesting excess bleeding risk in women was associated with differences in comorbidities rather than an independent biological association. However, when interpreting the results of the TWILIGHT trial, it is important to notice that with regard to Bleeding Academic Research Consortium (BARC) type 3 or 5 bleeding, the risk attenuation after adjustment for baseline risk was minimal, with a decrease of the hazard ratio from 1.57 (95% CI, 1.04-2.37) to 1.49 (95% CI, 0.96-2.32), suggesting additional unknown or unmeasured factors that may contribute to women’s increased risk for serious bleeding.