*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.