Abstract: A retrospective study was conducted on zoonotic and other infectious bacterial organisms from October 2010 to June 2011 from laboratory records of culture confirmed cases in human admitted to Dessie Hospital during the period of 2006/7 to 2011 in Dessie Regional Health Research Laboratory. The main objective of the study was to illustrate the epidemiology of the most frequent zoonotic and other infectious bacterial organisms and assess the potential risk factors in the area. Out of 2395 individual cases, 1186 were found to be infected with one or more infectious bacterial organisms, indicated by a prevalence rate of 49.52% (95% CI: 47.52-51.52%). There was significant association between prevalence of bacterial infection (χ² = 8.8953; p = 0.031) within age groups and those individuals below 12 years old were found to be affected 1.37 fold (OR = 1.37; 95% CI: 1.08-1.75) than those individuals above 35 years old. But there was no significant association between prevalence of bacterial infection (p = 0.0538) and sex groups. The highest proportion of bacterial infection was recorded during the year 2009/10 and least record was documented in the year 2010/11 with a prevalence of 13.57 and 8.1%, respectively. A relative increase in disease was observed during the study period. Future studies of zoonotic disease should standardize diagnostic ascertainment and incorporate therapeutic response and outcome, particularly the selection and effects of antibacterial therapy. Ongoing advances in bacteriology to improve clinical decision making for complex microbial infections is urgently required.