An alteration of pathophysiology in critically ill patients, resulting in pharmacokinetic change, are important factors in determining the therapeutic outcome of β-lactam antibiotics. The aims of this study were to reveal the population PK and assess the probability of target attainment (PTA) of imipenem in order to be able to optimize dosing recommendations for treatment of patients with VAP. Patients were randomized into two groups: Group I received a 0.5-h infusion of 0.5 g every 6 h (q6h) for nine doses and Group II received a 4-h infusion of 1 g q8h for seven doses. A Monte Carlo simulation was performed to determine the PTAs of achieving 20% T >MIC (exposure time during which the free drug concentration remains above the minimum inhibitory concentration (MIC)) and 40% T >MIC . The volume of distribution (Vd) and total clearance (CL) of imipenem were 15.89 L and 20.87 L/h, respectively. The high PTA (≥90%) achieving 40% fT >MIC for MICs of 4 μg/mL was observed when imipenem was administered by a 4-h infusion of 1 g q8h or 1 g q6h. These findings showed that the values of Vd and CL of imipenem in this patient population were greater than the values obtained from healthy subjects. A higher than recommended dosage regimen of imipenem may be required to optimize pharmacodynamic targets.