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Background: Screening and brief interventions (SBI) in primary healthcare are cost-effective in risky drinkers, yet they are not offered to all eligible patients. This qualitative study aimed to provide more insight into the factors and mechanisms of and implementation strategies work or do not work why, how, for whom under what circumstances in increasing SBI. Methods: Semi-structured interviews were conducted between February and July 2014 with 40 GPs and 28 nurses in Catalonia, the Netherlands, Poland, and Sweden. Participants were purposefully selected from the European Optimising Delivery of Healthcare Interventions (ODHIN) trial. This randomised controlled trial evaluated the influence of training and support, financial reimbursement and an internet-based method of delivering advice on SBI. Amongst them were 38 providers with a high screening performance and 30 with a low screening performance from different allocation groups. Realist evaluation was combined with the Tailored Implementation for Chronic Diseases framework for identification of implementation determinants to guide the interviews and analysis. Transcripts were analysed thematically with the diagram affinity method. Results: Training and support motivated SBI by improved knowledge, skills and prioritisation. Continuous provision, sufficient time to learn intervention techniques and to tailor to individual experienced barriers, seemed important T&S conditions. Catalan and Polish professionals perceived financial reimbursement to be an additional stimulating factor as well, as effects on SBI were smoothened by personnel levels and salary levels. Structural payment for preventive services rather than a temporary project based payment, might have increased the effects of financial reimbursement. Implementing e-BI seem to require more guidance than was delivered in ODHIN. Despite the allocation, important preconditions for SBI routine seemed frequent exposure of this topic in media and guidelines, SBI facilitating information systems, and having SBI in protocol-led care. Hence, the second order analysis revealed that the applied implementation strategies have high potential on the micro professional level and meso-organisational level, however due to influences from the macro- level such as societal and political culture the effects risks to get nullified. Conclusions: Essential determinants perceived for the implementation of SBI routines were identified, in particular for training and support and financial reimbursement. However, focusing only on the primary healthcare setting seems insufficient and a more integrated SBI culture, together with meso- and macro-focused implementation process is requested. Trial registration: ClinicalTrials.gov. Trial identifier: NCT01501552. [ABSTRACT FROM AUTHOR]