Background: Adolescents' vulnerability to HIV/AIDS infection arises from their immaturity, sexual risk behaviours as well as factors of a social, economic, cultural and gender nature (Ministério da Saúde, 2012). Adolescence is a st age of the lifecycle in which managing const ant and daily temptations and gaining and maintaining healthy lifestyles are difficult tasks and a test of the powers of self-regulation. Purpose: T o analyze the relationship between socio-demographic variables, school context, lifest yles, self-regulation skills and knowledge about HIV/AIDS in adolescents in secondary education in Portugal. Methods: Quantitative, cross-sectional, analytical, descriptive and correlational study with a sample of 971 adolescents in secondary education. T he evaluation protocol includes a socio-demographic questionnaire, the school context, lifest yles, the Reduced Quest ionnaire of Self-regulation (Carey, Neal & Collins, 2004 adapted by Castillo & Dias, 2009), Knowledge About AIDS Scale for Adolescents (Zimet et al., 1989). Results: sample of 50.80% boys, ages equal to or less than 16 years (43.40%), residing in rural areas (66.40%), cohabiting with parents (77.30%). T he correlations indicate that among adolescents' knowledge about AIDS and the subscale setting goals there is a positive and significant correlation (r = 0.224, p = 0.000), as well as the overall value of the Self-regulation Scale. Significant and negative correlations are presented for the impulse control subscale (r = -0.257, p = 0.000) and not significant to the overall self-regulation value (r = -0.041, p = 0.099), ranging in reverse, meaning that more knowledge about AIDS, better self-regulation with regard to impulses subscale. Conclusion: Self-regulated behaviour requires control of immediate needs, mobilization of thoughts, feelings and behaviours for purposes of long-term health, especially with regard to the prevention of HIV/AIDS.