Background: Antimicrobial resistance remains a global challenge. In Germany, the national health agenda supports measures that enhance the appropriate, guideline-oriented use of antibiotics. The study “Converting Habits of Antibiotic Use for Respiratory Tract Infections in German Primary Care (CHANGE-3)” aimed at a sustainable reduction of antimicrobial resistance through converting patterns of prescribing and use of antibiotics and an increase in health literacy in primary care patients, practice teams, and in the general public. Embedded in a cluster-randomized trial of a multifaceted implementation program, a process evaluation focused on the uptake of program components to assess the fidelity of the implementation program in the CHANGE-3 study and to understand utilization of its educational components. Methods: A mix of qualitative and quantitative methods was used. Semi-structured telephone interviews were conducted with General Practitioners, Medical Assistants, patients treated for respiratory tract infection and outreach visitors who had carried out individual outreach visits. A two-wave written survey (T1: 5 months after start, T2: 16 months after start) was conducted in general practitioners and medical assistants. Qualitative data were analyzed using thematic framework analysis. Descriptive statistics were used to analyze survey data. Results: Uptake of intervention components was heterogenous. Across all components, the uptake reported by General Practitioners varied from 20% to 88% at T1 and 31% to 63% at T2. Medical Assistants reported uptake from 22% to 70% at T1 and 6% to 69% at T2. Paper-based components could by and large be integrated in daily practice (64% to 90% in T1; 41% to 93% in T2), but uptake of digital components was low. A one-time outreach visit provided thematic information and feedback regarding actual prescribing, but due to time constraints were received with reluctance by practice teams. Patients were largely unaware of program components, but assumed that information and education could promote health literacy regarding antibiotics use. Conclusions: The process evaluation contributed to understanding the applicability of the delivered educational components with regards to the appropriate use of antibiotics. Future research efforts need to identify the best mode of delivery to reach the targeted population. Trial registration: ISRCTN, ISRCTN15061174. Registered 13 July 2018 – Retrospectively registered, http://www.isrctn.com/ISRCTN15061174