Purpose To evaluate the prevalence and risk factors associated with horizontal strabismus in children and adolescents in South Korea. Methods A total of 5,935 children and adolescents 5±18 years of age who participated in the fourth and fifth Korean National Health and Nutrition Examination Survey (KNHANES IV-V) from July 2008 to December 2011 were evaluated and the prevalence of horizontal strabismus was estimated. Univariate and multivariate logistic regression analyses were conducted to determine the association between demographic, socioeconomic and clinical risk factors and clinically significant exodeviation (>15 prism diopters [PD]) and esodeviation (> 10 PD). Results Among 5,935 eligible subjects, 84 subjects had clinically significant exodeviation and 13 had clinically significant esodeviation. The overall prevalence of clinically significant horizontal strabismus was 1.6% (95% confidence interval [CI], 1.2±2.1): 1.3% (95% CI, 1.0±1.7) for clinically significant exodeviation and 0.3% (95% CI, 0.1±0.6) for clinically significant esodeviation. Clinically significant exodeviation was associated with amblyopia (adjusted odds ratio [aOR], 6.45; 95% CI, 2.14±19.44), family history of strabismus (aOR, 4.91; 95% CI, 1.71±14.08) and astigmatism > 1.0 D (aOR, 1.84; 95% CI, 1.13±2.98). Clinically significant esodeviation was associated with hyperopia (aOR, 12.16; 95% CI, 1.31±113.04) and amblyopia (aOR, 4.70; 95% CI, 1.12±19.81). Other demographic, socioeconomic, and clinical variables were not associated with strabismus. Conclusion This study provides data on the prevalence and independent risk factors for clinically significant exodeviation and esodeviation in a representative population of children and adolescents in South Korea.