Introduction: MyPKFiT and the Web-Accessible Population Pharmacokinetic service—Hemophilia (WAPPS-Hemo) are web-based population-based applications developed for helping physicians individualize and optimize replacement therapy. Although MyPKFiT is intended for Octocog alfa and Rurioctocog alfa pegol use only, the WAPPS-Hemo is applicable to all factor VIII concentrates. Aim: To compare MyPKFiT and WAPPS-Hemo as dosing tools for optimizing treatment of patients with severe haemophilia A on regular prophylaxis with Octocog alfa in a real-world setting. Methods: Fourteen patients with severe haemophilia A (median age 30.8 years; range 20–71) were enrolled. The FVIII activity was measured twice after a regular dose of Octocog alfa by the chromogenic and the one-stage assays. PK analyses were performed using each tool and dosing estimations to reach trough levels of 1%, 3% or 5% after 48 h. Findings were calculated and compared. Results: The two PK algorithms yielded similar t½ independent of the type of FVIII assay used. However, there were significant differences in the time to reach 1%, 3% and 5%. The WAPPS-Hemo generated 10–12 h longer time to a trough of 1% and up to 4 h for the troughs of 3% and 5%. Accordingly, the doses estimated by WAPPS-Hemo for a daily regimen were between 28% and 100% of those proposed by MyPKFiT. Conclusions: MyPKFiT and WAPPS-Hemo provided similar half-life estimations for Octocog alfa independent of the FVIII assay used. The doses suggested by WAPPS-Hemo to reach specific troughs were overall lower, which may have implications for treatment optimization.