Background The students in University enjoy the freedom of living outside the guidance of their parents; if this is not managed properly it increases the likelihood to have of risky sexual behaviour and HIV infection. It is imperative to monitor HIV among young people in universities for proper and timely action.

Objective This research objective was to determine the prevalence of HIV infection among Dire Dawa university students and identify risk factors for HIV sero-positivity.

Method A cross sectional study with internal comparison was conducted among students of Dire Dawa. A self administrated questionnaire was used to gather relevant information and blood test was conducted for HIV antibody. The two information were linked anonymously. Qualitative data was collected using Focus group discussion.

Result The prevalence of HIV was 2.5% (95% CI 1.5, 3.5) (2.3% for female and 2.7% for male) with no significant difference between male and female. The students having sexual affair with same sex or both sexes were significantly 10.45 times (95% CI 1.93, 56.41) to be exposed to HIV than those having sexual affairs with only opposite sex. Having non-regular partner is significantly associated with HIV positivity among sexually active (OR = 6.35 and 95% CI 2.2, 18.3). Drinking alcohol and chewing chat was a risk factor for commencing sexual intercourse among male with (OR = 2.73 and 95% CI 1.72, 4.33) and (OR = 2.02 and 95% CI 1.19, 3.42) respectively.

Conclusion The students in the university are at risk of HIV infection, it is necessary to target them earlier in the high school and later when joining college by building their knowledge and skill to avoid risky sexual behaviour.