Background: Youths in universities are at high risk of STIs and SRH problems in Ethiopia. However, students did not perceive themselves at risk of STI/HIV infection though reports showed they were sexually active, had multiple sexual partners and reported symptoms of STIs. Having recognized the threat posed by SRH problems, this study aimed to assess the SRH experiences, knowledge, and problems among university students at Ambo University in Ethiopia. Methods: A cross-sectional study was conducted in Ambo University main campus from January to February 2015 using mixed approach of quantitative (survey) and qualitative (in-depth interview) methods. Proportionate stratified sampling technique was used to select 400 survey respondents and purposive sampling was employed to identify 10 in-depth interviewees. The quantitative data was coded, entered to SPSS and descriptively analyzed, while the qualitative data was categorically organized, repeatedly reviewed and thematically analyzed. Results: Mean age during first sex of 17.29 +/- SD 2.21 and mean number of past 12 months regular sexual partners of 1.36 +/- SD 0.505 were recorded. Only 21.1% of survey respondents perceived themselves to be at risk of HIV. Almost all survey respondents ever heard of STIs (94.5%) and HIV/AIDS (98%), and 89.4% knew modern contraceptives such as pills (64.8%) and condoms (56.8%). Despite awareness of STIs including HIV/AIDS, more than one fifth (22.8%) had any of the STIs in the past one year. Although the quantitative data showed unwanted pregnancy (5%) and abortion (2.5%) existed in the campus minimally, high rates of unwanted pregnancy and unsafe abortion were reported in the qualitative data. Conclusions: SRH/STIs were problems among students of the university. Although students knew about STIs, the STI infection rate in the past year was quite high, and was almost as high as the percentage of students who reported sexual activity in the past year. Though reported by a minority of students, unwanted pregnancy and unsafe abortion may also be a problem. The university thus needs to launch a program directed towards STIs and SRH problems, particularly among female students.