Recent evidence suggests that nursing students face barriers in translating into practice their acquired knowledge during a palliative care (PC) course. However, it is not known whether qualified health care workers exposed to this course experience the same barriers. This study aimed at reporting facilitators and barriers encountered in implementing a PC program in sub-Saharan Africa. This is a longitudinal study on an experimental single group of senior nurses and medical doctors enrolled into a pilot regional PC program, with an intensive 3-day PC initiator’s course, and dedicated to constitute a mobile PC unit equipped with PC tools and oral liquid morphine in 18 hospitals. Quantitative and qualitative data were collected through two focus groups discussion of 21 participants each, 10 individual critical incident interviews and observation to evaluate challenges faced in putting into practice PC knowledge. Qualified health care workers exposed to this program were able to translate knowledge into practice in their local settings. They were able to better understand and manage PC patients in their daily practice. However they reported difficulties in providing quality care: eligibility criteria, announcement of bad news, morphine management. Problems were also observed in the organization of service like difficulties in filling patients’ file, lack of reporting, and implication into other overwhelming hospital activities, with some of these said to originate from the hospital administration. This study suggests that qualified health care workers exposed to PC course can capitalize on it for use in their practice for patients in need. However the various barriers reported and observed are mostly inherent in the complexity of PC provision for holistic care, and the involvement of the hospital administrative authorities for quality service. It suggests the need for capacity building training for workers and a strong advocacy intended for any end-decision maker while implementing a PC program.