Background: Hypothyroidism is a prevalent endocrine disorder among elderly individuals. Attaining an optimal level of self-care ability is a vital component of integral nursing management. Aim: Determine the effect of illness perception and medication adherence on self-care ability of elderly patients with hypothyroidism. Method: A descriptive correlational research design was used. This study was carried out in geriatric and endocrinology outpatient clinics at Specialized Medical Hospital, Mansoura University. A purposive sample of 239 elderly patients with hypothyroidism were enrolled in the study. Data was collected using; the mini-mental state examination scale, demographic and health-related data structured interview sheet, the brief illness perception questionnaire, the 8-item Morisky medication adherence scale, and the self-care ability scale for the elderly. Results: 88.3% of the studied elderly with hypothyroidism had low self-care ability (53.67± 6.57) while 53.6% had moderate illness perception (42.77±4.05), and 65.20% had low medication adherence level. Conclusion: Illness perception and medication adherence were significant predictors for self-care ability in elderly patients with hypothyroidism. Recommendation: Develop self-care programs aimed at improving the self-care practice of elderly patients with hypothyroidism taking into consideration the study associated factors.