Background: Type 1 Diabetes Mellitus (T1DM) impacts health-related quality of life (HRQoL). Cross-sectional studies suggest that low levels of vitamin D (VD) may impair HRQoL, however, the effect of VD supplementation on quality of life in patients with T1DM has not yet been clarified. The objective of the study was to evaluate the effects of high-dose VD supplementation on HRQoL in patients with T1DM. Methods: We performed a prospective interventional study with 64 patients supplemented with high doses of cholecalciferol (4,000 IU/day for patients with 25-OH-vitamin D [25(OH)D] between 30 and 60 ng/mL, and 10,000 IU/day for those with 25(OH)D below 30 ng/mL) for 12 weeks. HRQoL was assessed with EuroQol instruments (EQ-5D and EQ-VAS). Results: There was an improvement in global EQ-5D index at the end of vitamin D supplementation. Analysing only the EQ-5D domains, we observed particularly an improvement in mobility (1.3 ± 0.6 versus 1.1 ± 0.3, p <0.01). Evaluating possible outcome influencing variables, we detected a reduction in albuminuria at the end of the trial, without changes in BMI, lipids, blood pressure, glycemic control, insulin doses and in peripheral diabetic neuropathy. We also found a correlation between final albuminuria and the dimensions: mobility (r = 0.6; p <0.01), personal care (r = 0.7; p <0.01), pain and discomfort (r = 0.6; p <0.01) and habitual activities (r = 0.6; p <0.01), suggesting an association between albuminuria reduction and the impact of VD supplementation on HRQoL. Conclusion: Our data showed that high doses of cholecalciferol supplementation can improve HRQoL in patients with T1DM, and the reduction of albuminuria seems to be an important factor in this context.Trial registration: ISRCTN, ISRCTN32601947. Registered 3 June 2017 - Retrospectively registered, http://www.isrctn.com/ISRCTN32601947