Background: Tracking the changing epidemiology of Transfusion Transmissible Infections (TTIs), including Immunodeficiency virus (HIV), is critical to attaining the Sustainable Development Goals (SDG.3.3) milestones and deadlines. This study assessed the dynamics associated with Blood Donation and TTIs among blood donors at the Akatsi South Municipality in the Volta Region of Ghana. Methods: This was a haemovigilance study, designed to retrospectively evaluate secondary data on 2,588 blood donors in Akatsi South District Hospital from 2014 to 2019. Data was collected, managed and quality controlled done electronically using Microsoft Visual Basics and STATA. The trends of TTIs were determined using frequentist and descriptive statistics, and 95% confidence intervals using the Clopper Pearson test. Results: The prevalence of TTIs was 8.0%. The prevalence of HIV as well as HBV and HCV, was 3.8%, 3.2%, and 1.0% respectively. For female hosts, the prevalence was 7.4% (HIV), 4.2 % (HBV), and 1.6% (HCV). For Male-host, the rates were 3.1% (HIV), 3.5% (HBV), and 1.0% (HVC). Donors aged 15-19years were most infected at rates of 13.2% (HIV), 4.7% (HBV), and 1.9% (HCV). Conclusion: About 57(2.4%) and 3(1.2%) of 2380 blood donated were TTIs false negatives and false positives respectively. In addition to being a driver of TTIs among blood donors in this study, the HIV prevalence among teenagers was significantly above the regional and national rates. These rates have programmatic and research implications. A relatively higher sensitive blood transfusion screening method is urgently needed to prevent the transfusion of TTIs false negative blood in Akatsi Municipal Hospital