Background Skin cancers represent a major challenge within the ever growing group of long time surviving organ transplant recipients (OTR) world wide. Especially UV‐induced non‐melanoma skin cancers (NMSC) like invasive squamous cell carcinomas (SCC) and actinic keratoses (AK), and basal cell carcinoma (BCC), outnumber every other form of cancer in organ transplant recipients. Despite encouraging reports of protective effects of broad‐spectrum sunscreens in immunocompetent patients, evidence for the prevention of NMSC in immunocompromised patients is still missing.

Objectives To assess preventive effects of regular sun‐screen use on AK, SCC and BCC in chronically immunocompromised organ transplant recipients.

Methods Hundred and twenty matched (age, sex, skin type, graft, transplant duration, previous post‐transplant skin malignancies) organ transplant recipients (40 heart, 40 kidney, 40 liver grafted) were recruited for this prospective, single‐center study. Both groups received equally written and oral information on sun protection measures. Sixty patients were provided with a free broad spectrum study‐sunscreen (SPF > 50, high‐UVA absorption) for daily application of 2 mg cm⁻² to the head, neck, forearms, and hands.

Results All 120 patients completed the 24 months study. Within this 24 month study interval 42 of the 120 patients developed 82 new AK (−102 sun screen group vs. + 82 control; P < 0·01), 8 new invasive SCC (0 vs. 8; P < 0·01) and 11 BCC (2 vs. 9; ns). In spite of equal numbers of AK at baseline, a marked difference in favor of the intent‐to‐treat sunscreen group was recorded after 24 months (89 vs. 273; P < 0·01, mean difference 3·07 [1·76–4·36]) and the lesion count was significantly lower as compared to the initial visit (89 vs. 191; P < 0·01, mean difference 1·7 [0·68–2·72]). With an average of 5·6 applications per week throughout the 24 months the study sunscreen was generally well tolerated. Serum 25‐hydroxy vitamin D levels as marker for vitamin D status were decreased in all patients without adequate substitution and 25(OH)D was found to be lower in the sunscreen‐group as compared to the control group (mean value 53 ng mL⁻¹ vs. 60 ng mL⁻¹).

Interpretation Regular use of sunscreens, as part of a consequent UV‐protection strategy, may prevent the development of further AK and invasive SCC and, to a lesser degree, BCC in immune‐compromised organ transplant recipients.