Purpose: Apixaban is recommended for patients with atrial fibrillation. Although routine monitoring of plasma concentrations is not typically advised, factors such as ethnicity, sex, and comorbidities can influence these levels. Our study analyzed the plasma apixaban concentrations (PAC) in patients to explore whether these levels, along with underlying conditions, offer enhanced insights for risk stratification. Methods: This study analyzed 49 patients with atrial fibrillation who had been taking apixaban for over a month, examined factor Xa levels within 6 h post-administration, and correlated PAC with clinical characteristics such as age, body weight, estimated glomerular filtration rate (eGFR), presence of heart failure, and bleeding events. Results: The mean plasma concentration of apixaban in all patients was 160.3 ± 77.5 ng/mL. Those taking apixaban 5 mg twice daily had higher plasma concentrations than those taking 2.5 mg twice daily (191.2 ± 75.3 ng/mL vs.137.2 ± 72.0 ng/mL, p = 0.014). Among the patients receiving a reduced dose, renal function and heart failure were significantly associated with plasma concentrations. No factors were associated with the plasma concentrations in patients receiving the standard dose. Notably, reduced-dose patients with heart failure had plasma concentrations comparable to those of individuals receiving the standard dose and exhibited a higher incidence of bleeding than the other groups. Conclusions PAC measurement revealed that apixaban dosages, classified based on age, body weight, and eGFR, were generally effective. Nonetheless, heart failure may increase plasma levels and correlate with an increased bleeding risk in Korean patients on reduced doses. Therefore, tailoring apixaban prescriptions to account for heart failure and other comorbidities may enhance treatment efficacy.