Abstract. The present study aimed to prepare, optimize, and evaluate Tapentadol hydrochloride controlled porosity osmotic pump (CPOP) and to achieve the drug release at nearly zero-order. The CPOP was prepared by the coating of polymers (Eudragit RSPO and RLPO) on a directly compressed core tablet. A Box-behnken experimental design was applied to optimize the parameters for CPOP. The optimized batch was characterized for in vitro drug release study, effect of pH, osmolarity and agitation intensity, and surface morphology and stability study. In vivo pharmacokinetic studies were performed on New Zealand white rabbits for CPOP and marketed tablet. All the batches showed a drug release ranging from 29.87 to 56.92% after 12 h; and from 59.64 to 99.96% after 24 h. There was no change in the drug release pattern at different pH and agitation intensities. The drug release was found to decrease with increasing osmolarity of dissolution media.An in vivo study showed a higher mean residence time, area under the curve, and biological half-life (T 1/2 ) than the marketed tablet with low rate of elimination (Ke) and a 2.35-fold increase in relative bioavailability. The result showed that the amounts of sodium chloride and PEG 400 were contributing positively while the number of coats was negatively affecting the drug release. The drug release was found to be independent of physiological conditions. The stability testing showed that the prepared CPOP was stable for 3 months at accelerated conditions. The prepared CPOP was found to deliver Tapentadol hydrochloride at zero-order for up to 24 h.