In the present work, monolithic matrix transdermal systems containing tramadol HCl were prepared using various ratios of the polymer blends of hydroxy propyl methyl cellulose (HPMC) and Eudragit S 100 (ES) with triethyl citrate as a plasticizer. A 32 full factorial design was employed. The concentration of HPMC and ES were used as independent variables, while percentage drug release was selected as dependent variable. Physical evaluation was performed such as moisture content, moisture uptake, tensile strength, flatness and folding endurance. In-vitro diffusion studies were performed using cellulose acetate membrane (pore size 0.45 μ) in a Franz’s diffusion cell. The concentration of diffused drug was measured using UV-visible spectrophotometer (Jasco V-530) at λ max 272 nm. The experimental results shows that the transdermal drug delivery system (TDDS) containing ES in higher proportion gives sustained the release of drug.