These studies were designed to determine the effect of hydroalcoholic gel system (lower alkanol concentration: 40-60%) compared to general hydrogel system (lower alkanol concentration: 10-35%) on transdermal delivery of piroxicam and its anti-inflammatory activity. Piroxicam was incorporated into a hydroalcoholic gel and a hydrogel containing polymers, solvents, and cosolvents. The pH of gel was about 6.3-7.3 and the solvent mixtures were composed of water and various concentrations of ethanol (35, 40, 50, and 60%). For the in vitro study, the skin permeation of piroxicam from the gel formulations was investigated using Franz modified diffusion cells fitted with hairless mouse skin. For the in vivo study, the anti-inflammatory activity of hydroalcoholic gel was compared to other commercial products (piroxicam hydrogel and ketoprofen hydrogel) in rat and human. The anti-inflammatory activity was determined using carrageenan induced foot edema model in rat. For the clinical study, it was evaluated from determining efficacy and acceptability with 98 patients suffering from musculoskeletal pain. A novel piroxicam hydroalcoholic gel was successfully formulated in the range of 40-50% of ethanol as solvent, more than 10% of propylene glycol, 5% of $Transcutol^{circledR}$ and 1 % of benzyl alcohol. The skin permeation of piroxicam using hydroalcoholic gel system was greater than that of general hydrogel system $(flux;:;139.1-148.2;{mu}g/cm^2/hr;vs.43.0-84.5 {mu}g/cm^2/hr)$ in vitro. In carrageenan-induced edema model, the anti-inflammatory activity of hydroalcoholic gel was better than that of piroxicam hydrogel for edema inhibition (75.1 % vs. 62.9%, p<O.01). In clinical study, each visual analogue of pain scale (improvement point: 15.57 point vs. 3.61 point, p<0.05) and global acceptability assessment (satisfied patients: 76.2% vs. 47.7%, p<0.05) of new hydroalcoholic gel was significantly increased compared to ketoprofen hydrogel. The inclusion of piroxicam to the hydroalcoholic gel system was found to improve significantly the skin permeation in vitro and the anti-inflammatory activity in vivo.