Children with asthma and obesity are more likely to have lower vitamin D levels, but the optimal replacement dose is unknown in this population. The objective of this study is identifying a vitamin D dose in children with obesity-related asthma that safely achieves serum vitamin D levels of ≥ 40 ng/mL. This prospective multisite randomized controlled trial recruited children/adolescents with asthma and body mass index ≥ 85% for age/sex. Part 1 (dose finding), evaluated 4 oral vitamin D regimens for 16 weeks to identify a replacement dose that achieved serum vitamin D levels ≥ 40 ng/mL. Part 2 compared the replacement dose calculated from part 1 (50,000 IU loading dose with 8,000 IU daily) to standard of care (SOC) for 16 weeks to identify the proportion of children achieving target serum 25(OH)D level. Part 1 included 48 randomized participants. Part 2 included 64 participants. In Part 1, no SOC participants achieved target serum level, but 50-72.7% of participants in cohorts A-C achieved the target serum level. In part 2, 78.6% of replacement dose participants achieved target serum level compared with none in the SOC arm. No related serious adverse events were reported. This trial confirmed a 50,000 IU loading dose plus 8,000 IU daily oral vitamin D as safe and effective in increasing serum 25(OH)D levels in children/adolescents with overweight/obesity to levels ≥ 40 ng/mL. Given the critical role of vitamin D in many conditions complicating childhood obesity, these data close a critical gap in our understanding of vitamin D dosing in children.