Abstract : Introduction: Sickle Cell Disease (SCD) is a chronic disease that affects millions of people globally, causing chronic pain episodes and complications that significantly impact patients' self-care capacity. Empowerment-Based Interventions (EBI) have been shown to improve self-efficacy, self-care capacity, and Health-Related Quality of Life (HRQOL) among patients with chronic diseases. The aim of this study is to investigate the effect of EBI on self-efficacy, self-care capacity, and HRQOL among adults with SCD. Methods: A randomized controlled trial, two groups, pre-posttest study was conducted at two primary health care centers in Bahrain using a cluster sampling technique. A sample of 68 adults with SCD were randomly assigned to two groups. The EBI was implemented through structured small-group discussion sessions, individualized consultations, and follow-up sessions. Individualized consultations for self-management were done by adopting the 5A model (Assess, Advise, Agree, Assistant, and Arrange). Weekly communication was done to check the patient's progress, and both groups were re-evaluated for self-efficacy, self-care capacity, and HRQOL after one month. Results: The results showed a significant improvement in the EBI group regarding their ability to keep doing most of the day-to-day activities as the mean score was 4.31±0.79 compared to 3.47±0.89 in the control group (P<0.001). Similarly, the application of the EBI enabled adults with SCD to reduce pain by using methods other than taking extra medication (P<0.001). Regarding self-care, adults who received the EBI exhibited a higher capacity for self-care as their mean score was 4.32±0.35 compared to 3.49±0.48 in the control group (P<0.001). The EBI also enabled them to develop a capacity for self-care (4.02±0.42) compared to the routine health care (3.02±0.52). As for the HRQOL, a noticeable improvement in the general health among patients in the EBI compared to the control one (P=0.02). Discussion: The findings of this study support the effectiveness of EBI using the 5As model in improving self-efficacy, self-care capacity, and HRQOL among patients with SCD. The use of individualized consultations and follow-up sessions allowed for tailored interventions that addressed the specific needs of each patient. The weekly communication also allowed for monitoring of patients' progress and any necessary adjustments to the intervention. The significant improvement in self-care capacity and the ability to keep doing day-to-day activities has important implications for patients' daily lives and their ability to manage their disease. The reduction in pain without the need for extra medication is also an important benefit. Conclusion: In conclusion, this study highlights the effectiveness of EBI using the 5As model in improving self-efficacy, self-care capacity, and HRQoL among patients with SCD. Healthcare providers should consider adopting this intervention in their practice to improve the quality of life of patients with SCD. Further research is needed to explore the long-term effects of EBI and to identify the optimal delivery methods for this intervention.