Three novel, simple, accurate and rapid methods have been developed and validated for estimation of tapentadol hydrochloride in bulk and in laboratory tablet sample. In RP- HPLC method, elution was achieved in isocratic mode using combination of 50mM phosphate buffer pH 3.62 and acetonitrile in ratio of 70:30 (% v/v) with 0.1% triethylamine and using HiQ Sil C8 column having specification, 250 x 4.6 mm and 5μm particle size. The flow rate was 1 ml/min and detection was done at 285 nm. UV-Spectrophotometric estimation of tapentadol was carried out at 272 nm. Third method consists of quantification of tapentadol using Folin-Ciocalteu reagent in presence of 20% sodium carbonate solution. The blue colour chromogen formed is measured at wavelength of maximum absorption 750 nm for tapentadol against reagent blank. All three developed methods were validated according to ICH guidelines. Furthermore assay results obtained by three methods were compared statistically as well.