Objectives: To assess the efficacy of an oral high-dose cholecalciferol regimen in correcting vitamin D deficiency (VDD) in adolescents and to explore potential predictive factors on the response to treatment. Methods: This is a retrospective chart review conducted in the Adolescent Outpatient Clinic, Geneva University Hospitals, Switzerland. One hundred-three otherwise healthy vitamin D deficient [serum 25-hydroxyvitamin D, 25(OH)D, level <50 nmol/L] adolescents (mean age 16.6) attending the clinic between 1 January 2016 and 31 December 2018 received 150,000 IU of oral cholecalciferol every month for 3 months (cumulative dose of 450,000 IU). We measured the change in serum 25(OH)D levels pre- and post-treatment and the achievement of serum 25(OH)D level post-treatment ≥75 nmol/L. Results: The mean serum 25(OH)D level increased by 320%, from 26 nmol/L at baseline to 83 nmol/L at the end of the study (P < .001). The rise was significantly higher for patients initially tested in the winter/spring (mean 65 nmol/L) compared with those initially tested in the summer/autumn (mean 48 nmol/L) (P < .003). No clear relationship was found between the response to treatment and the vitamin D status at baseline. The effect of age, gender, origin and body mass index was not statistically significant. Conclusions: The present intermittent high-dose regimen is effective in treating VDD in healthy adolescents without significant variations in response between different subgroups.