The study assessed the effects of Management Information Systems (MIS) on the organizational performance of the Catholic University College of Ghana (CUCG) and recommended the most optimal and efficient ways possible towards addressing the University’s data structure issues which are not consistent across its faculties and departments. A descriptive survey design was employed with a sample size of 125 which was obtained through simple random technique. The main instrument for the data collection was structure questionnaire. The data was analysed using the Statistical Product for Service Solution (SPSS) version 23.0. Data collected were analyzed using descriptive statistics, frequencies, means, and standard deviation. The findings of the study revealed that challenges exist in the existing MIS practices but they do not significantly affect employees’ performance. The study concludes that management information system indicators such as system quality, information quality, and user satisfaction have a positive and significant influence on organizational performance of CUCG. The study recommends that management should ensure that adequate budget is allocated towards building a robust, effective and an integrated MIS infrastructure that would enhance the quality of management decisions in the University.