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The study objective was to evaluate the population pharmacokinetics and pharmacodynamics of piperacillin and tazobactam administered by prolonged infusion in obese and nonobese patients. Twenty‐seven patients (total body weight [TBW], 60 to 211 kg; body mass index [BMI], 19.6 to 72.9 kg/m²) received 4.5 or 6.75 g every 8 hours, infused over 4 hours, and serum concentrations were measured at steady state. Population pharmacokinetic parameters were estimated using NONMEM, and Monte Carlo simulations were performed for three 4‐hour dosing regimens to calculate probability of target attainment (PTA) at ≥50% fT>MIC.A 1‐compartment linear‐elimination model best fit the pharmacokinetic data for piperacillin and tazobactam. Creatinine clearance (CRCL), TBW, and BMI were significantly associated with piperacillin pharmacokinetics, and CRCL was significantly associated with tazobactam …