Purpose: Therapeutic vancomycin levels are difficult to maintain in severe pneumonia patients who are receiving IV vancomycin therapy while on continuous venovenous hemofiltration (CVVH). The objective of this study was to determine the pharmacokinetics and maintenance dose recommendations of vancomycin in severe pneumonia patients receiving CVVH. Methods: A prospective study was conducted in the intensive care unit of a university hospital. Ten severe pneumonia patients receiving vancomycin and CVVH treatment were determined the initial and steady-state pharmacokinetics of vancomycin. CVVH was performed in mixed predilution and postdilution mode with a blood flow rate of 180 mL/min and an ultrafiltrate flow rate of 30–40 mL/kg/h. Group A received an initial dose of 500 mg only, whereas group B received 500 mg every 12 h until steady state is achieved. Serum and ultrafiltrate were collected over 12 h after infusion of vancomycin. Results: After initial dosing, the mean sieving coefficient (SC) was 0.72 ± 0.02, and CVVH clearance (CL, 1.35 ± 0.03 L/h) constituted 60.55% ± 13.69% of total vancomycin clearance (CL, 2.36 ± 0.72 L/h). When steady state was reached, the SC of the patients was 0.71 ± 0.03, and the CL (1.34 ± 0.06 L/h) accounted for 66.96% ± 6.05% of the CL (2.03 ± 0.27 L/h). The recommended maintenance dose for vancomycin in severe pneumonia patients was 400–650 mg every 12 h, which was calculated based on CL, to achieve a trough concentration of 15–20 mg/L at steady state. Conclusions: Single administration or multiple administration does not affect SC and CL. Owing to therapeutic vancomycin levels is difficult to maintain in severe pneumonia patients who are receiving IV vancomycin therapy while on CVVH, close monitoring of serum trough concentrations is required.