Background: Blood transfusion remains a critical component of modern medical care, but it carries the risk of transmitting infections such as HIV, Hepatitis B (HBV), Hepatitis C (HCV), syphilis, and malaria. Ensuring blood safety through rigorous screening is essential for public health. This study aims to assess the trends and prevalence of transfusion-transmissible infections (TTIs) among blood donors in North India over a two-year period at MaharshiMarkandeshwar Medical College and hospital, Sadopur, Ambala. Materials and Methods: A retrospective analysis of blood donor records from January 2022 to December 2023 was conducted. Data from hospital blood bank records were reviewed, covering an estimated 80donors per year. Donors underwent routine serological screening for HIV, HBV, HCV, syphilis, and malaria using ELISA and rapid diagnostic tests. Statistical analysis was performed to determine the prevalence trends and potential risk factors among donors. Results: Out of approximately 160 donors over two years, TTIs were detected in 12.5% of cases. The most common infection was HBV (5.6%), followed by HCV (3.1%), HIV (2.5%), and syphilis (1.3%). No cases of malaria were recorded. The prevalence of TTIs was higher among replacement donors compared to voluntary donors. Male donors constituted 85% of the study population, with a mean age of 32 years. A slight decline in TTIs was observed in the second year compared to the first. Conclusion: The study highlights a considerable prevalence of transfusion-transmissible infections in North Indian blood donors, emphasizing the need for stringent donor screening and awareness programs. Strengthening pre-donation counselling and implementing advanced testing methods can further enhance blood safety and reduce the risk of transmission.