BACKGROUND: Alterations in the vitamin D axis have been implicated in chronic wounds, but their role in leprosy-related trophic ulcers (TU) is unclear. This study compared serum vitamin D levels and VDR FokI (rs2228570) polymorphism between leprosy patients with and without TU, assessed their association with ulcer presence, and examined the correlation between vitamin D levels and ulcer severity. METHODS: This case-control study involved 82 adult leprosy patients (41 with TU, 41 without) treated at a tertiary referral hospital in Jakarta, Indonesia. Serum 25-hydroxyvitamin D [25(OH)D] levels were measured using chemiluminescence assay, and FokI polymorphism was analyzed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Ulcer severity was evaluated using the Pressure Ulcer Scale for Healing (PUSH). Associations were assessed through bivariate and multivariate analyses. RESULTS: Patients with TU had significantly lower mean serum 25(OH)D levels than those without TU (13.14 vs. 20.18 ng/mL, p < 0.001). The homozygous mutant FokI genotype (ff) was more frequent in the TU group (p = 0.043). In multivariable analysis, both low vitamin D status (adjusted odds ratio [aOR] 4.15; 95% confidence interval [CI] 1.41-12.24; p = 0.010) and the FokI polymorphism (aOR 7.86; 95% CI 1.80-34.36; p = 0.006) remained independently associated with TU. Vitamin D levels showed a weak inverse correlation with PUSH scores (r = -0.312, p = 0.047). CONCLUSIONS: Lower serum vitamin D status and the FokI polymorphism were independently associated with TU in leprosy, and a weak inverse correlation was observed between serum vitamin D levels and ulcer severity. While genetic variation is non-modifiable, vitamin D status represents a potentially modifiable factor; hence, these findings suggest that assessment of vitamin D status may be considered as part of comprehensive ulcer care in leprosy. Copyright: © 2026 Halim et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.