A novel transdermal drug delivery system with the eutectic mixture of lidocaine and prilocaine was developed. The permeation of lidocaine and prilocaine proportionally increased as the weight ratio of poly(vinyl alcohol) to poly(acrylic acid) changed from 1:1 to 7:1. However, the adhesive property of the matrix significantly degraded over the ratio of 5:1. The incorporation of humectants in the matrix had a noticeable effect on the permeation of lidocaine and prilocaine. The flux of lidocaine increased as the ratio of lidocaine in the eutectic mixture increased. The permeation rate decreased significantly from the cataplasm containing 3.5:1 and 4:1 ratio of lidocaine to prilocaine due to recrystallization. When total drug concentration of the cataplasm with the ratio of 3:1 increased from 1.33 to 4 % against adhesive gel weight, the permeation of both lidocaine and prilocaine increased. However, crystallization was observed beyond 2.66 % w/w of combined drug load. Enhancers were not effective in the present study as most of the enhancer showed very low or no enhancement effect. No significant changes in the appearance and the drug content in the cataplasm were observed for 3 months.