Introduction: This study reports on physicians’ experiences in conducting end-of-life conversations with elderly patients who suffered from multiple co-morbidities (MCM). Our hypothesis was that both the lack of prognostic certainty and the lack of good communication tools contributed to physicians’ discomfort with conducting EOL conversations with patients and families of patients with these conditions especially when compared with patients and families of patients who had a single, clear terminal diagnosis (e.g. pancreatic cancer). Methods: Focus group questions were semi-structured and explored three general themes: (1) differences between having an end-of-life conversation with patients/families with MCM versus those with a single, terminal diagnosis; (2) timing of the end-of-life conversation; and (3) approaches to the end-of-life conversation. Results: Three themes emerged: (1) It is more difficult for them to have EOL conversations with patients with MCM and their families, as opposed to conversations with families and patients who have a clear, terminal diagnosis. (2) In deciding when to raise the subject of EOL care, participants reported that they rely on a number of physical and/or social signs to prompt these discussions. Yet a major reason for the difficulty that providers face in initiating these discussions with MCM patients and families is that there is a lack of a clear threshold or prompting event. (3) Participants mentioned three types of approaches to initiating EOL conversations: (a) direct approach, (b) indirect approach, (c) collaborative approach. Conclusion: Prognostic indicies and communication scripts may better prepare physicians to facilitate end-of-life conversations with MCM patients/families.