Background Many general practitioners (GPs) are willing to provide end-of-life (EoL) home care for their patients. International research on GPs’ approach to care in patients’ final weeks of life showed a combination of palliative measures with life-preserving actions.Aim To explore the GP’s perspective on life-preserving versus “letting go” decision-making in EoL home care.Design Qualitative analysis of semi-structured interviews with 52 Belgian GPs involved in EoL home care.Results Nearly all GPs adopted a palliative approach and an accepting attitude towards death. The erratic course of terminal illness can challenge this approach. Disruptive medical events threaten the prospect of a peaceful end-phase and death at home and force the GP either to maintain the patient’s (quality of) life for the time being or to recognize the event as a step to life closure and “letting the patient go”. Making the “right” decision was very difficult. Influencing factors included: the nature and time of the crisis, a patient’s clinical condition at the event itself, a GP’s level of determination in deciding and negotiating “letting go” and the patient’s/family’s wishes and preparedness regarding this death. Hospitalization was often a way out.Conclusions GPs regard alternation between palliation and life-preservation as part of palliative care. They feel uncertain about their mandate in deciding and negotiating the final step to life closure. A shortage of knowledge of (acute) palliative medicine as one cause of difficulties in letting-go decisions may be underestimated. Sharing all these professional responsibilities with the specialist palliative home care teams would lighten a GP’s burden considerably.Key PointsA late transition from a life-preserving mindset to one of “letting go” has been reported as a reason why physicians resort to life-preserving actions in an end-of-life (EoL) context. We investigated GPs’ perspectives on this matter.Not all GPs involved in EoL home care adopt a “letting go” mindset. For those who do, this mindset is challenged by the erratic course of terminal illness.GPs prioritize the quality of the remaining life and the serenity of the dying process, which is threatened by disruptive medical events.Making the “right” decision is difficult. GPs feel uncertain about their own role and responsibility in deciding and negotiating the final step to life closure.