Levetiracetam is a second-generation antiepileptic drug and distributed ubiquitously in the central nervous system. The extended-release formulation of levetiracetam was developed to provide patients with the convenience of once-daily dosing, to improve drug compliance and tolerability. The objective of this study was to evaluate the pharmacokinetics and safety of levetiracetam extended-release (ER) tablets in healthy Chinese subjects following single and multiple doses. Two panels of 34 healthy subjects were enrolled. Trial 1 was a two-way crossover between levetiracetam ER tablets and immediate-release (IR) tablets under fasting conditions. Trial 2 was a four-way crossover single-dose study between levetiracetam ER fasted and ER with food. Intake of single and multiple levetiracetam ER tablets resulted in a 42.3% lower maximum plasma concentration (C (max)) and a 33.6% lower minimum steady-state plasma concentration (C (ss min)) than IR tablet intake, while the median time to C (max) (t (max)) was significantly delayed. The 90% CI of the ER/IR ratios for area under the curve (AUC) from zero to last measurable sample (AUC(0-t) ), AUC from zero to infinity (AUC(0-a) ), AUC at steady state (AUC(ss), tau = 24 h), C (max) at steady state (C (ss max)) and average concentration at steady state (C (ss av)) were contained within the 80-125% range of bioequivalence. The C (max) and AUC were dose proportional across the dose cohorts. Following a high-fat meal, levetiracetam ER tablets resulted in a 14.4% higher C (max). The 90% confidence interval (CIs) of the fed/fasted ratios for C (max) and AUC were entirely contained within the 80-125% range of bioequivalence acceptance, except the t (max) was delayed (P < 0.05). The most frequent treatment-emergent adverse events were somnolence, dizziness and thirst. After single and multiple doses, the absorption of levetiracetam ER was equal to IR, the t (max) was significantly delayed, and the C (max) and C (ss min) were significantly decreased. Food did not affect the absorption of the levetiracetam ER tablet, but the C (max) increased and the t (max) was delayed. The levetiracetam ER tablet was well tolerated and found to be dose proportional from 500 to 2000 mg in healthy Chinese subjects.