Oxybutynin inhibits contraction of the detrusor muscle in the overactive bladder by binding to muscarinic M-3 receptors and blocking acetylcholinergic activation. The transdermal oxybutynin system, applied twice weekly, delivers continuous oxybutynin over a 96-hour patch wear period. The transdermal route of administration avoids the extensive first-pass metabolism of oxybutynin to its active metabolite, N-desethyloxybutynin. In two well designed trials in patients with overactive bladder, transdermal oxybutynin 3.9 mg/day decreased the number of incontinence episodes and increased average voided volume to a significantly greater extent than placebo. Urinary frequency was improved to a significantly greater extent with transdermal oxybutynin than with placebo in one trial but not the other. There was no significant difference between transdermal oxybutynin and extended-release oral tolterodine for any of these endpoints. Health-related quality-of-life improvements with transdermal oxybutynin were shown in patients with overactive bladder in the open-label MATRIX trial, as demonstrated by significant improvements in all domains of the King's Health Questionnaire. Transdermal oxybutynin is generally well tolerated in patients with overactive bladder. The majority of patients who discontinued transdermal oxybutynin treatment in two pivotal trials did so because of application-site reactions. However, none discontinued treatment because of dry mouth.