The purpose of this study was to examine the determinants of students’ choice of program at the Senior High School (SHS) level in the Gomoa East District of the Central Region of Ghana. It was a quantitative study underpinned by the positivist paradigm. The descriptive survey design was employed for the study. A self-developed questionnaire was used to collect data from a sample of 229 for the study. Multiple linear regression was used to analyze the data. The study found that students’ general academic performance was the best predictor of students’ choice of program followed by advice from colleagues or peers of students. The study, therefore, recommended that the Ghana Education Service (GES) and Management of SHSs, should work on equipping students with learning and research skills to enable them to enhance their self-efficacies and general academic performance.