1519 Background: Skin cancers are the most common malignancies in OTR. Topical 5% 5-FU has been used to successfully treat squamous cell carcinoma (SCC) in situ and actinic keratosis (AK). Capecitabine, an orally-administered prodrug of 5-FU, in combination with interferon was shown to be effective in the treatment of advanced SCC of the skin. This study was to determine the efficacy of low-dose capecitabine in secondary prevention of the skin cancers in OTR. Methods: OTR who developed recurrent skin cancers, SCC, and/or basal cell carcinoma (BCC), were given low-dose capecitabine 1g/m2 divided in two daily doses, day 1–14 of 21-day treatment cycle. Skin surveillances were performed by dermatologists every 1 to 3 months. Cumulative incidence rates of SCC, BCC, and AK before and after treatment were scored and statistically compared for each patient with a non-parametric Wilcoxon signed-rank test. Age and number of transplants were assessed with the Spearman non-parametric correlation analysis for their impact on the outcome. Results: 14 patients (12 males and 2 females) were enrolled with median age of 55 (range 40–73). 11 patients received kidney, two lung and one liver, one heart and one pancreas transplant. Two patients received double organ transplants. Mean incidence rates of SCC, BCC, and AK before treatment were 0.45, 0.05, and 4.99 lesions per month, respectively. Mean incidence rates of SCC, BCC, and AK after treatment were 0.22, 0.04, and 2.80 lesions per month, respectively. The differences in incidence rates of SCC, BCC, and AK before and after treatment were 0.24, 0.02, and 2.08 lesions per month with p value of 0.048, 0.844, and 0.151, respectively. Age and the number of transplants were not significantly related to the change in incidence rates for all skin lesion types. Six of the total of 14 patients experienced grade 3/4 toxicities, including mucositis (2), hand-foot syndrome (3), fatigue (2), nausea (1), diarrhea (2), hyperuricemia (1), and anemia (1), and all six needed capecitabine dose reduction or stopping therapy. Conclusions: Oral capecitabine significantly decreases the incidence rates of recurrent SCC in OTR and has manageable toxicity. No significant financial relationships to disclose.