Background: Homeopathic aggravation is a temporary worsening of existing symptoms following the administration of a correct homeopathic prescription. The aim of this study was to explore and compose criteria that may differentiate homeopathic aggravations from adverse effects. Material and Methods: A qualitative approach was employed using focus group interviews. 2 interviews, with 11 experienced homeopaths, were performed in Oslo, Norway. The practitioners have practiced classical homeopathy over a period of 10–32 years. Qualitative content analysis was used to analyze the text data. The codes were defined before and during the data analysis. Results: We found that aggravations were subtle and multifaceted events. Moreover, highly skilled homeopaths are required to identify and report aggravations. Adverse effect may be defined as an ‘undesirable effect of a remedy’. This definition is pragmatic, flexible, and more in line with the holistic paradigm that the homeopaths represent. 8 criteria that distinguish aggravation from adverse effect were found. Highly sensitive persons hold a unique position regarding safety, as it is important to identify these patients in order to treat them correctly and avoid undesirable effects of the treatment. Conclusion: This study rigorously explored homeopaths’ views and experience on aggravation and adverse effects. The 8 criteria developed in this study may ensure patient safety and support therapists in identifying an ‘undesirable effect of a remedy’.