BACKGROUND: In 2009, 665 patients underwent total knee replacements (TKRs) at the Norfolk and Norwich University Hospitals NHS Foundation Trust (NNUH), representing nearly 1% of the national total. Pain control following the operation can be poor, and this can cause poor mobilization and potential long-term adverse events. Although high levels of pain are not associated with patient dissatisfaction, brief periods of pain may lead to neuronal remodeling and sensitization. Patient controlled oral analgesia (PCOA) may improve pain relief; however, the evidence to date has been inconclusive. Patient directed self management of pain (PaDSMaP) is a single center randomized controlled trial, which aims to establish if patient self-medication improves, or is equivalent to, treatment as usual and to create an educational package to allow implementation elsewhere. METHODS/DESIGN: Patients eligible for a TKR will be recruited and randomized in the outpatient clinic. All patients will undergo their operations according to normal clinical practice but will be randomized into two groups. Once oral medication has commenced, one group will have pain relief administered by nursing staff in the usual way (treatment as usual; TAU), whilst the second group will self manage their pain medication (patient directed self management of pain; PaDSMaP). Those recruited for self-medication will undergo a training program to teach the use of oral analgesics according to the World Health Organization (WHO) pain cascade and how to complete the study documentation. The primary endpoint of the trial is the visual analogue scale (VAS) pain score at 3 days or discharge, whichever is sooner. The follow-up time is 6 weeks with a planned trial period of 3 years. The secondary objectives are satisfaction with the management of patient pain post-operatively whilst an inpatient after primary TKR; overall pain levels and pain on mobilization; satisfaction with pain management information provided; global outcomes, such as quality of life (QOL) and activities of daily living (ADLs); time to mobilization and whether time to mobilization is associated with frequency of adverse events, improvements in QOL, ADLs and pain at 6 weeks after the operation; incidence of adverse events; quantity and type of pain medications used whilst an inpatient; the acceptability of PaDSMaP and/or TAU protocols for patients and the healthcare professionals involved in their care; to investigate the health-related costs associated with a PaDSMaP system; and to estimate the cost-effectiveness of PaDSMaP compared to TAU. TRIAL REGISTRATION: Current Controlled Trials ISRCTN: 10868989.