A new transdermal therapeutic system has been developed, in which estradiol is dispersed in the adhesive matrix. Gynecologists from 10 Swedish cities recruited 265 healthy women >50 years of age with climacteric complaints into a randomized trial. The objectives of the study were to compare the effects of treatment with the new matrix system and a registered reservoir system. Both patches administer 50 μg/day of 17-beta-estradiol transdermally. Significantly fewer women on the new patch noted erythema, itching, rubbing of the patch on clothes, rustling of the patch, and problems removing the protective lining. The matrix patch also adapted better to the skin and fell off in significantly fewer cases than the reservoir patch. The physician was unaware of the treatment allocated to the patient. Clinic visits were scheduled during treatment-free periods. Patch sites were examined by a study nurse, independently of the clinician. Overall assessment of effectiveness by the investigators favored the new matrix patch, even though efficacy variables suggested equivalence.