Transmissible Infections (TTI's) are a cause of significant burden on health care facilities by imposing a threat of infection transmission through disease reservoirs in asymptomatic donors. This eventually leads to a serious challenge in acquiring blood bags in a country like Pakistan where transfusion dependent disease are of high prevalence. The objective of this study is to determine the seroprevalence of TTI's in blood donors in Rawalpindi District through a multi-center approach. This is an observational descriptive retrospective study based on 6 transfusion centers in the Rawalpindi District. The time frame of the study was from January 2015 to December 2018. A total of 223,242 donors were consecutively included and data on donor type, the purpose of transfusion, and seroprevalence (HBV, HCV, HIV, Syphilis, and Malaria) were collected through a structured questionnaire and laboratory investigation results. The collected data were entered in SPSS version 21.0 for analysis. The seroprevalence of blood borne infections was 7,897 (3.537%) of which HBV, HCV, HIV, Syphilis and Malaria accounted for 2410 (1.080%), 3105(1.391%), 0(0.000%), 2017 (0.933%) and 365 (0.171%), respectively. Reactive samples reduced from 4.850% to 3.537% over 4 years, while there was a rise of 37.478% of blood donors from 2015 to 2018. The total number of voluntary donors and replacement donors was 22079 (9.890%) and 201156 (90.107%), with a rising incidence in voluntary donors from 2015 to 2018. A considerable number of donor bags were transfused to Thalassemia, Anemia, Leukemia and Hemophilia patients, 28156 (12.612%). This number also showed increasing rates from 11.654% to 14.017%. In conclusion, our study suggests that the risk of transmission through transfusion is still considerable. Targeting donors with a low-risk profile, a screening questionnaire, an ample supply of quality screening tests, and awareness campaigns for the diseases in question must be carried to further decrease the risk of transmission of TTIs in Pakistan.