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Background: Self-care of adolescents with congenital heart disease (CHD) is one of the challenges of the health care system. CHD is a common chronic disease that affects the quality of life (QoL) and self-efficacy of adolescents. This study compares the effectiveness of self-care education by face-to-face method and video clip (VC) on self-efficacy and QoL in late adolescents with CHD. Methods: This research was a non-randomized clinical trial. A total of 111 late adolescents aged 18 to 21 years with CHD referred to Rajaie Cardiovascular, Medical, and Research Center in Tehran, Iran, were recruited by convenience sampling and non-randomly assigned to either control, face-to-face (F2F), or VC groups (37 subjects in each group). The F2F group participated in two educational sessions (each lasted 35-45 minutes) with an interval of one week, and the VC group received a 90-minute video to watch at home. The study data were collected before (T1) and two months after the intervention (T2), using the Generalized Self-Efficacy (GSE) scale and World Health Organization’s Quality of Life Questionnaire (WHOQOL-BREF) and analyzed in SPSS version 19 software using the Chi-square test, Fisher test, paired t test, Scheffé test, and ANOVA. The significance level was set at P0.05). Conclusion: Self-care education through F2F and VC significantly affects the self-efficacy and QoL of late adolescents. Such educational programs can greatly reduce the possible complications of the disease by empowering this group.