Adolescents and young adults (15-24 yrs.) have poorer HIV clinical outcomes than adults. Despite this, there is minimal data on individual-level factors such as self-efficacy towards antiretroviral adherence among perinatally infected adolescents living with HIV in sub-Saharan Africa. Our study examined the interaction between antiretroviral treatment adherence self-efficacy and other psychosocial factors among adolescents receiving care in Nairobi, Kenya. We enrolled perinatally infected Adolescent Living with HIV (ALWHIV) 16-19 yrs. who were accessing care routinely at the HIV clinic. We measured self-reported ART adherence (7-day recall) and defined optimal adherence as >95%, and conducted a regression analysis to identify independently associated factors. Mediation analysis explored interactions between the psychosocial variables. We enrolled 82 ALWHIV median age 17 (IQR 16,18) who had been on ART for a median age of 11 yrs. (IQR 7,13). Sixty-four per cent (52) of the ALWHIV reported optimal adherence of >95%, and 15% reported missing doses for three or more months. After controlling for the other covariates, self-esteem, high viral load and an adherence level > 95% were significantly associated with adherence self-efficacy. Self-esteem was significantly associated with adherence self-efficacy and social support (p<0.001 and p=0.001), respectively. The paramed test indicated that the association between self-efficacy and adherence was mediated by self-esteem with a total effect of OR 6.93 (bootstrap 95% CI 1.99-24.14). Adherence self-efficacy was also mediated by self-esteem in developing adherence behavior. Interventions focused on increasing adherence among ALWHIV should include self-esteem building components.