The quantitative study explores the relationship between enrollment type (regular students vs. distance students) and academic performance among students at C.K. Tedam University of Technology and Applied Sciences and University for Development Studies in Ghana. Utilizing regression analysis and ANOVA, the research examines the impact of enrollment type while controlling for prior academic achievement (WASSCE grades) and university attended. Results reveal that enrollment modality significantly affects academic performance, with distance students exhibiting slightly lower GPAs compared to regular students. Furthermore, prior academic achievement emerges as a strong predictor of GPA, emphasizing the importance of pre-university academic performance. However, the specific university attended and the interaction between enrollment type and university were not significant predictors of GPA. These findings underscore the complex interplay between enrollment type, prior academic achievement, and academic performance in Ghanaian universities, providing valuable insights for educational policy and practice.