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Aim: In this study, we aimed to assess cosmetic use and associated negative effects among female graduate students at the universities. Subject and methods: A multicenter cross-sectional study design was used to assess cosmetic utilization and any associated negative consequences among 338 female graduate students from June 1 to June 30, 2022. Descriptive and inferential statistics were computed using the Statistical Package for Social Sciences (SPSS) version 25. Results: All female students used cosmetics, and the prevalence of cosmetic-related adverse effects was 65.1%. Hair breakage was the leading adverse effect, followed by skin allergies and soreness. The determinants of cosmetic-related adverse effects were as follows: previous urban residence before joining the university (P-value: 0.034, AOR = 2.43, 95% CI: 1.06–5.52); greater than 500 birr monthly pocket money (P-value: 0.011, AOR = 2.76, 95% CI: 1.26–6.05); number of cosmetics used per day: 3–5 cosmetics/day (P-value: 0.001, AOR = 7.41, 95% CI :2.29–24.03); cosmetics left on more than 5 days before cleansing (P-value: 0.001, AOR = 10.12, 95% CI: 4.3–35.8); the practice of label-reading (P-value: 0.016, AOR = 0.38, 95% CI: 0.17–0.83); and health confirmation as selection criteria (P-value: 0.01, AOR = 0.03, 95% CI: 0.006–0.23). Conclusion: All of the female students were found to be using cosmetic products, and two thirds had developed cosmetic-related adverse effects. It is basically advisable to have rational cosmetic utilization.