Abstract Objectives: Over the past decade, numerous obesity-specific pharmacokinetic (PK) models and dosage regimens have been developed. However, it is unclear whether vancomycin PKs differ between obese and other patients after accounting for weight, age, and kidney function. In this study, the authors investigated whether using obesity-specific population PK models for vancomycin offers any advantage in accuracy and precision over using a recently developed general-purpose model. Methods: Vancomycin plasma concentrations in a cohort of 49 obese patients (body mass index [BMI] > 30 kg/m), not previously used in the development of any of the evaluated models, were used to validate the performance of four obesity-specific models and a general model. Bias and imprecision were calculated for the a priori and a posteriori predictive performance. Results: The bias of the a priori prediction was lowest for one of the obesity-specific models (-1.40%) and that of the general model was a close second (-7.0%). The imprecision was lowest for the general model (4.34 mg/L). The predictive performance for the a posteriori predictions was best for the general model, both for bias (1.96%) and imprecision (2.75 mg/L). Conclusions: The results of the external validation of vancomycin PK in obese patients showed that currently available obesity-specific models do not necessarily outperform a broadly supported general-purpose model. Based on these results, the authors conclude that there is no advantage in using vancomycin PK models specifically tailored to obese patients over the general-purpose model reported by Colin et al.