Attention-deficit/hyperactivity disorder (ADHD) is one of the most common behavioral disorders in childhood. It continues into adulthood in up to 65% of patients. Methylphenidate (MPH) is one of the most commonly used pharmacological treatments for ADHD. The osmotic-release oral system (OROS) formulation of MPH is an extended-release pharmaceutical form that delivers MPH in a controlled manner over a 12-h period, allowing management of symptoms for a full day. OROS-MPH has many advantages over immediate-release MPH, such as avoiding clinical rebound, being easy to take, increasing treatment adherence and reducing the risk of abuse. OROS-MPH has been approved in the USA and Europe for the treatment of ADHD in children, but it has only been approved for the treatment of adults in the USA and Canada. This review summarizes evidence from various clinical studies assessing the efficacy and safety of OROS-MPH in different clinical samples of adults with ADHD, including samples with the most common comorbidities found in ADHD patients. The studies are classified according to their design characteristics as randomized, controlled trials or open trials. Data on dosing, treatment adherence and other clinical parameters relevant for the use of OROS-MPH in adults with ADHD are also reported and discussed. © 2009 Expert Reviews Ltd.