OBJECTIVE: The aim of this study was to review factors that influence serum 25(OH)D when patients are given vitamin D supplements. METHODS: From a comprehensive search of all randomized controlled clinical trials with vitamin D3 supplementation available on PubMed up to November 2011, we selected 33 with 43 treatment arms that included at least 30 adult participants. The achieved pooled mean difference (PMD) and 95% confidence intervals (CIs) were calculated using the random-effects models. Meta-regression and subgroup analyses were performed for prespecified factors, including dose, duration, baseline serum 25(OH)D, and age. RESULTS: With a mean baseline serum 25(OH)D of 50.4 nmol/L, PMD was 37 nmol/L (95% CI, 33-41) with significant heterogeneity among studies. Dose (slope: 0.006; P < 0.001), trial duration (slope: 0.21; P < 0.001), baseline serum 25(OH)D (slope: -0.19; P < 0.001), and age (slope: 0.42; P < 0.001) independently influenced vitamin D response. Similar results were found in studies with a mean baseline serum 25(OH)D <50 nmol/L. In subgroup analyses, the PMD was higher with doses >/=800 IU/d (39.3 nmol/L) after 6 to 12 mo (41.7 nmol/L), with baseline 25(OH)D <50 nmol/L (39.6 nmol/L), and in adults aged >80 y (40.5 nmol/L). CONCLUSION: This meta regression indicates that a higher increase in serum levels of 25(OH)D in adults is found with a dose of >/=800 IU/d, after at least 6 to 12 mo, and even when baseline 25(OH)D is low and in adults >80 y.