Blood transfusion is a life-saving procedure for millions in current medical and surgical practices. However it also has the risk of transmitting Transfusion Transmitted Infections (TTIs) like HIV, hepatitis B and C, syphilis, malaria etc. In India, it is mandatory to test blood units for HIV 1 and 2, hepatitis B, hepatitis C, syphilis and malaria. The whole blood and component units that are reactive should be discarded. The present study was done retrospectively from January 2016 to December 2018 (a 3 years study) in the Department of Transfusion Medicine and Immunohematology, Nizam’s institute of Medical Sciences, Hyderabad, Telangana State, India. During these three years the total donors were 55,306. Voluntary donors were 13.20 % and replacement donors were 86.80 %. A total of 148 donors were reactive for syphilis. Predominant age range reactive for syphilis was 26-35 years (66.89 %), followed by 36-45 years (19.59 %). 148 (0.27 %) donors were reactive for Syphilis. Number of replacement donors positive for syphilis were 147 whereas the number of voluntary donors positive for syphilis were only one. 142 donors were married and 6 were unmarried. All the syphilis reactive donors were males. 95 donors were from urban areas, whereas 53 were from rural areas. Increasing trend of syphilis reactivity was observed in our geographical area. Voluntary blood donations are safer than replacement. Education and public awareness programs would go a long way in suppressing these infections and thereby preventing TTIs and also wastage of precious blood units.