BackgroundMultimorbidity is a common phenomenon among patients treated in general practices. Key challenges within this group include functional difficulties, polypharmacy, treatment burden, fragmentation of care, reduced quality of life and increased health care utilization. These problems cannot be solved in the short consultation time of a general practitioner (GP) since there is an increasing shortage of GPs. In many countries, advanced practice nurses (APNs) are successfully integrated into primary health care for multimorbid patients.The objective of this study is to examine whether the integration of APNs in the primary care of multimorbid patients in Germany leads to optimized care of the target group and to a reduction in the workload of the GPs.MethodsThe intervention includes the integration of APNs into the care for multimorbid patients in general practice for twelve months. Qualifications for APNs include a master's level academic degree and 500 hours of project-specific training. Their tasks include in-depth assessment, preparation, implementation, monitoring and evaluation of a person-centred and evidence-based care plan.In this nonrandomized controlled trial, a prospective multicentre mixed methods study will be performed. The main inclusion criterion was the cooccurrence of three chronic diseases. For data collection in the intervention group (n= 817), routine data from health insurance companies and association of statutory health insurance physicians (ASHIP) will be used, as well as qualitative interviews. In addition, the intervention will be assessed through documentation of the care process and standardized questionnaires using a longitudinal design. The control group (n= 1634) will receive standard care. For the evaluation, routine data from health insurance companies are matched at a ratio of 1:2.Outcomes will be measured using emergency contacts and GP visits, treatment costs, health status of the patients and the satisfaction of parties involved.The statistical analyses will include Poisson regression to compare outcomes between the intervention and control groups. Descriptive and analytical statistical methods will be used in the longitudinal analysis of the intervention group data. Cost analysis will compare total costs and subgroup costs between the intervention and control groups. Qualitative data will be analysed using content analysis.DiscussionChallenges to this protocol could include the political and strategic environment as well as the planned number of participants.Trial registrationDRKS00026172 on DRKS.