Background: The ongoing Coronavirus Disease 19 (COVID-19) pandemic has caused an increased burden on healthcare organizations and public health resources. Objective: This study aimed to examine the potential impact of home-based self-isolation on health-related outcomes of patients suffering from COVID-19, toassess patients' and household contacts' compliance to physicians' instructions while isolated at home, and to explore predictors affecting home-based self-isolation compliance. Methods: A cross-sectional analytical study of 393 mild/moderate adult cases of COVID-19 patients referred to home isolation by Cairo University Hospital through the period from June 1^st to September 30, 2020. Results: The proportion of patients admitted to the hospital while isolated at home was 76 (19.3%). When examining the factors contributing to hospital admission among the home isolation instructions measures, we found that 74.5% of those who abide by the home isolation rules were not hospitalized compared to 25.5% hospitalized (P-value<0.001; OR= 11.8; 95% CI: 3.65–38.59). The infection rate among household contacts while patients isolated at home was 38.42%. About 66.8% of those who abided by the home isolation instructions did not infect contacts compared to 33.2% who got infection (P-value=0.001; OR= 2.207; 95% CI: 1.404–4.807). Significant predictors for compliance with home-based isolation instructions were the presence of hypertension, previous hospitalization, and absence of chronic liver diseases. Conclusion: Compliance with isolation instructions and conforming to infection and control procedures are important factors to decrease hospital visits and infection rates among household contacts.