Background: Non-prescription medicines (NPMs) may be misused, abused and lead to dependence. Aims and methods • To determine the prevalence of self-reported NPM misuse, abuse and dependence in the general population and to explore factors predictive of misuse or abuse using a cross-sectional postal survey (n=411). • To identify the perceived barriers and enablers to seeking treatment for NPM dependence using qualitative semi-structured interviews with individuals dependent on NPMs (n=8). • To establish how NPM dependence is managed by specialist clinicians using an online survey (n=83) and to identify the perceived barriers and enablers to providing treatment using qualitative semi-structured interviews with a subset of survey respondents (n=11). Results A response rate of 43.4% (411/946) was achieved for the general population survey. The lifetime prevalence was 19.3% for NPM misuse, 4.1% for abuse and 2% for dependence. Factors significantly predictive of misuse or abuse were younger age, having a long-standing illness requiring regular use of NPMs and ever having used illicit drugs or legal highs. The most frequently mentioned barriers to seeking treatment were insufficient knowledge about treatment and how to access it, and a perceived lack of services or healthcare professionals which could provide appropriate help. Most clinicians had encountered cases of NPM dependence and prescribed opiate replacement therapy to treat it. The most frequently identified barriers to providing treatment were limited resources or capacity and the challenges presented by individuals dependent on NPMs. Conclusion There is a need for greater awareness of the potential for NPM misuse, abuse and dependence among the general population and healthcare professionals. The general population should be made aware that treatment is available and how to access it. Healthcare professionals should be equipped to provide treatment or signpost individuals to appropriate services that will provide treatment.