Background: Anemia is the most common nutritional problem in adolescent girls and it has negative consequence on cognition, work performance and economic productivity. However, in the developing world there is limited evidence regarding the magnitude and determinants of anemia among adolescent girls. The current study highlights the burden of and factors associated with anemia in adolescent girls in Hadero district, Southern Ethiopia. Methods: A community based cross-sectional study was conducted in January, 2016 among adolescent girls 10-19 years old. A total of 407 subjects were selected using multistage cluster sampling technique. Hemoglobin level was determined from capillary blood using the HemoCue method. Factors associated with anemia (give the operational definition in bracket) were identified using bivariate and multivariate binary logistic regression analysis. The outputs of analyses are presented using adjusted Odds Ratio (AOR) with 95% Confidence Interval (CI). Result: The mean (±SD) of hemoglobin concentration adjusted for altitude was 13.7 + 1.2and ranged from 8 to 16.6g/dl. The overall prevalence of anemia was 15.2% (95%CI: 11.68%, 18.72%). Out of the total 400 adolescent girls 13.7% [95% CI: 10.33%, 17.06%] and 1.5% [95%CI: 0.3%, 2.7%] had mild and moderate anemia, respectively. low dietary diversity, (AOR=3.6, 95 % CI: 1.7, 7.7), long menstrual duration (AOR=6.4, 95%CI: 1.55, 27.0), malaria attack history (AOR=3.2, 95%CI: 1.4, 7.2) and over loaded physical work load (AOR=4.0, 95%CI: 1.7, 9.5), large family size (AOR=0.37,95% CI:0.16, 0.92) and low altitude (AOR=3.2, 95%CI: 1.23, 8.3) were significantly associated with anemia. Furthermore, prevalence of stunting and thinness were 21.3% and 16.5 % respectively. Conclusion : Anemia is a mild public health problem in the study area; increasing dietary diversity, Insecticide Treated Bed nets (ITNs) utilization and adolescent nutrition education are important strategies to reduce the burden of anemia.