Background: Most of the sexual initiation and sexual practice of adolescents begins atrnsecondary school which is very risky. Low self-esteem may predispose adolescents to sexual riskrnthrough negative schemata and attributions. However, not enough was done to assess the effectrnof self-esteem development in reduction of risky sexual behaviors among Ethiopian adolescents. rnObjective: The study aims to assess the magnitude of risky sexual behavior and its associationrnwith self-esteem and other covariates among in-school adolescents in Addis Ababa.rnMethods: Facility-based explanatory sequential mixed methods design was employed duringrnDecember 2020- February 2021. Self-administered questionnaire was used to collect quantitativerndata from 629 high school students selected using a multi-stage sampling method. Quantitativerndata was entered to Epi-data version 3.1 and exported to STATA version-15 for analysis.rnFrequency distributions of variables were tabulated. Bivariable and multivariable binary logisticrnregression analyses were performed and p-values less than 0.05 were considered to calibraternstatistical significance. The views of 18 qualitative participants selected by maximum variationrnsampling procedure were explored using an in-depth interview. The qualitative data were codedrnand classified into themes and sub-themes and findings were represented by way of a narrative.rnRESULTS: A total of 605 participated in the study (response rate of 96.2%). About 248(41%)rnof students reported that they ever had sexual intercourse. About 546(90.3%) of the students hadrnhigh self-esteem. The overall prevalence of risky sexual behavior was 160(26.5%). Perceptionrnabout the risk of STIs and pregnancy (AOR=2.34; 95% CI, 1.51-3.63), self-esteem (AOR=3.48;rn95% CI, 1.88-6.42), and school type (AOR=2.08; 95% CI, 1.14-3.79) were independentrnpredictors of risky sexual behaviors. The strong reasons for the practice of risky sexual behaviorsrnamong these adolescents were perception about sexual and reproductive health, low self-esteem,rnschool type, peer influence, substance use, pornography viewing and social media activities.rnCONCLUSIONS: Over one in four high-school students have risky sexual behavior. Riskrnperception, self-esteem and school type are significantly associated with risky sexual behavior.rnSexual and reproductive health programs for in-school adolescents should be tailored to addressrntheir specific needs by building friendly public policies; creating a supportive environment,rndeveloping personal skills, and reorienting the health services that help develop self-esteem andrnchange poor perceptions about STIs and pregnancy.