The purpose of the study was to investigate the effects of CAI on Upper Basic Education (Junior Secondary School) students’ achievement, interest and retention in health education. Quasi-experimental design was adopted in the study. Two research questions and three hypotheses guided the study. The study was conducted in Abia state of Nigeria. The population for the study consisted of 16381 Upper Basic Education (Junior Secondary School) students in the 36 public secondary schools in urban and rural locations in Umuahia Education Zone, Abia state. A sample of 414 Upper Basic Education (Junior Secondary School two) students was used for the study. The sample consisted of 229 urban schools’ students and 185 rural schools’ students. Also the sample consisted of 210 students in experimental group and 204 students in the control group. Health Education Achievement Test (HEAT) was validated by three research experts. HEAT yielded a reliability coefficient of .89 obtained through Kuder-Richardson’s formula 20 (KR-20) The researcher administered the instrument to the respondent’s hand to hand and received back the completed copies same way with the help of three trained (3) research assistants. Mean and standard deviation were used to answer the research questions while test of hypotheses was done using Analysis of Covariance (ANCOVA). Findings showed that the group taught CAI recorded higher mean scores than their counterparts in the control group, taught Health Education with lecture method. Furthermore, there was no significant effect and interaction between teaching methods and school location on the students’ achievement in Health Education. Based on the findings of the study, the following conclusions were drawn and recommendations made, which includes that the use of CAI for teaching secondary school health education should be adopted by all urban and rural secondary schools in Abia State.