We previously demonstrated that the active vitamin D hormone, 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3) and a cis-locked non-genomic analogue, protect skin cells from ultraviolet radiation (UV)-induced skin cell loss, DNA damage, immunosuppression and skin carcinogenesis. Here, we used low calcaemic analogue, 1α-hydroxymethyl-16-ene-24,24-difluoro-25-hydroxy-26,27-bis-homovitaminD3 (QW), which has some transactivating capacity and is approximately 80-100X less calcaemic than 1,25(OH)2D3. QW (0.1 – 10 nM) significantly (p < 0.05 - 0.01) reduced UV-induced DNA lesions (CPD) in skin fibroblasts and keratinocytes and reduced cell death after UV. Moreover, both 1,25(OH)2D3 and QW (1 nM) were equally effective in significantly (p < 0.01) increasing levels of tumour suppressive p53 in cultured human keratinocytes at 3 and 6 h after UV. In a hairless mouse model, both 1,25(OH)2D3 and QW (22.8 ρmol/cm2) reduced UV-immunosuppression from 13.7 ± 1.3 %. to 0.1 ± 1.1 % (p < 0.01) and 5.4 ± 1.5 % (p < 0.01) respectively. When tested alongside 1,25(OH)2D3 in a murine model of skin carcinogenesis. QW (22.8 ρmol/cm2) was not as effective as 1,25(OH)2D3 or a cis-locked analogue in reducing tumour formation or inhibiting tumour progression. It is possible that the dose required for QW to be effective as an anti-photocarcinogenesis agent in vivo is higher than for protection against the acute effects of UV, but the dissociation between clear acute photo-protective effects and limited long term photoprotection is as yet unexplained.