Purpose: One of the greatest challenges facing school nurses is that of identifying and using appropriate strategies to meet the health education needs of adolescents in regard to prevention of human immunodeficiency virus (HIV) and acquired immune deficiency syndrome (AIDS). This study examined the effects of HIV/AIDS preventive health education with parental involvement on students’ attitude toward HIV/AIDS prevention in Akwa Ibom State, Nigeria. Methods: The study population comprised students from three of nine secondary schools in the study area. The three schools were randomly assigned as Intervention Group 1 (IG1), involving nurses only; Intervention Group 2 (IG2), involving both nurses and parents (IG2); and a control group. A pretest/post-test intervention design was used. A 29-item, validated questionnaire was the instrument for data collection. Sampling involved multistage and stratified random technique to select 120 subjects from each of the three selected schools, with a total of 360 subjects representing 8.3% of the study population. From this number, 339 (94.2%) provided sufficient data for analysis. Data analysis involved analysis of covariance and the Scheffé post hoc test determined at the .05 significance level. Results: Results show significant effect of intervention on students attitudes toward preventive measures (F = 234.27, p < .001*). The intervention that involved nurses only was found to be a more potent strategy in providing favorable attitudes toward HIV/AIDS prevention (IG1 mean, 20.59; IG2 mean, 19.20; control mean, 12.34). Attitudes were influenced by older age but not by gender. Conclusion: Health education efforts aimed at improving HIV/AIDS-related attitudes should not only focus on children but also on parents so that they in turn could assist to improve on health workers’ efforts in educating the children.