Ultraviolet radiation (UVR) may contribute to multiple sclerosis (MS) outcome by a mechanism involving vitamin D and the vitamin D receptor (VDR). In 512 patients with MS duration of 10 or more years, we studied the association of VDR single nucleotide polymorphisms (A/G¹²²⁹, C/G³⁴⁴⁴, G/A³⁹⁴⁴, CC²⁰⁹⁶⁵, CC³⁰⁰⁵⁶, F/f³⁰⁸⁷⁵, C/T⁴⁸²⁰⁰, T/t⁶⁵⁰¹³) with outcome or disability. ff³⁰⁸⁷⁵ frequency was lower in cases with EDSS ≥ 6.0 than with scores < 6.0 (odds ratio = 0.38, 95% CI = 0.20–0.70). The association of ff³⁰⁸⁷⁵ with outcome was not mediated by cumulative exposure to UVR as assessed by questionnaire; low exposure (odds ratio = 0.42, 95% CI = 0.14–1.34) and high exposure (odds ratio = 0.34, 95% CI = 0.16–0.73).