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Introduction Subcutaneous infusion (SC) or hypodermoclysis is an old perfusion technique that is often used off-label although it has been shown to be effective. Acetaminophen (paracetamol) subcutaneous injection is performed in some centers despite the lack of conclusive evidence on its effectiveness. This study aims to evaluate the efficacy of subcutaneous infusion of Acetaminophen in the treatment of pain and fever in geriatrics and in palliative care and to determine its safety profile and possible side effects. Material and methods This experimental study was conducted between 2018 and 2019 on adult patients in palliative care or in geriatrics in several hospitals and nursing homes in Lebanon. Primary outcomes were change in temperature; change in pain score on the numerical rating scale (NS) or on the Algoplus scale after 60 min from the start of the infusion; and the appearance of local side effects at the infusion site. Changes in the various parameters at 30 min and 180 min were also evaluated as secondary outcomes. Results Thirty-one patients were included in the study, with a total of 120 doses of acetaminophen. At 60 min, the mean decrease in pain on the NS was 5.35 points, while the mean decrease in temperature was 0.79 degrees Celsius. At 60 min, 75%, CI = [47.62-92.73] of the patients who received acetaminophen for pain and 66.67%, CI = [38.38-88.17] of those who received it for fever had clinically significant improvement. The overall effect of subcutaneous acetaminophen, defined as any clinically significant effect on pain or fever, was 70.97%, CI = [51.96-85.78]. The overall effect at 30 min and at 180 min was 23.33%, CI = [9.93-42.28] and 87.10%, CI = [70.17-96.37], respectively. The side effects reported 30 min after the injection and observed after at least one of the doses were: local edema in 16 patients (51.61%), induration in one patient (3.23%), local pain in one patient (3.23%) and local heat in one patient (3.23%). At 180 min, only 2 patients (6.45%) still had edema at the infusion site. Conclusion Subcutaneous administration of acetaminophen is effective and well tolerated in geriatric and palliative care patients. It is appropriate when no other route is available, especially for home-based care. Comparative studies are needed to allow the expansion of this practice.