Background: Transfusion-transmitted infections (TTI) is still burden that continue to be a threat to safe transfusion practices of blood & components and one of the major problem in delayed transfusion hazards. In the present study prevalence and patterns of co-infections among voluntary and replacement donors were analyzed. Methods: This is descriptive study. Blood collected over a 6-year period were studied for the type of donation (voluntary or replacement), number of seroreactive cases and the number, type and distribution of co-infections among different type of donors. Results: Out of 127995 units of collected blood, 106755 (83.40%) were voluntary and 21240(16.60%) replacement donors of them 1463 were seroreactive. Out of 1463 seroreactive cases (1.14%) 128(0.10%), 137(0.11%),1025(0.8%) & 173(0.13%) were HIV, HCV, HBsAg (Hepatitis B surface antigen) & VDRL (Venereal Diseases Research Laboratory) respectively. 30 (0.02%) cases of seropositive samples showed more than one seroreactive reactions which were collected 14(0.06%) from replacement donors and 16(0.01%) samples from voluntary donors. Only 2 samples (0.001 %) of repeat donors show seropositivity. Conclusion: Possibilities of transfusion transmitted infections were more with replacement blood donors in comparison to voluntary blood donors. Repeat donors were safer than first time donors. Though the incidence was less, chances of multiple infections were still problems to the recipients. Proper history taking, screening and encouragement of blood donation would definitely reduce the chances of transfusion transmitted infection. Nepal Journal of Medical Sciences | Volume 02 | Number 01 | Jan-Jun 2013 | Page 3-8 DOI: http://dx.doi.org/10.3126/njms.v2i1.7643