Introduction:The aim of the present study was to understand the impact of comprehensive intervention program on self-esteem and self-efficacy among human immunodeficiency virus (HIV)-positive adolescents. Material and methods:Participants of the research were perinatally HIV-infected adolescent boys and girls, currently living in HIV care and support center. The study adopts a quasi-experimental non-equivalent control group design. Sample consisted of 97 adolescents (47 boys and 50 girls). Selfesteem was assessed using Morris Rosenberg's (1965) self-esteem scale, and self-efficacy was assessed using general self-efficacy scale (GSE) (1995) by Ralf Schwarzer & Matthias Jerusalem. It was hypothesized that there would be a significant improvement in the level of self-esteem and self-efficacy among participants of experimental group and no such improvement would be noticed in control group. Group intervention was conducted for experimental group focusing on four domains -physi cal, cognitive, affective, and social, for 44 hours spread over 6 months. Comprehensive intervention was implemented through innovative expressive strategies. Participants were assessed pre and post-intervention. Results were analyzed using correlated t-test for self-esteem and Wilcoxon signed-rank test for self-efficacy scores.Results: There is a significant improvement in the level of self-esteem (t = 21.154; p < 0.001) and self-efficacy (z = 6.036; p < 0.001) post-intervention in the experimental group, and no such improvement was observed on both the variables in control group. Conclusions:The current study reveal that post-intervention there is a significant improvement in the level of self-esteem and self-efficacy among HIV-positive adolescents.