Background: Although other immunosuppressive agents have been recently introduced (e.g., tacrolimus), it has been calculated that in the next decade about 1 million people will still be taking cyclosporin (CsA). The association between gingival overgrowth (GO) and the use of CsA is still not clear. In the present study we evaluated the prevalence and the degree of GO in a group of Italian renal transplant patients and the possible relationship between gingival lesions and demographic, oral, systemic, and pharmacological variables. Methods: One hundred twenty-one renal transplant recipients receiving immunosuppressive therapy with CsA were evaluated in this study. Patients were classified in two groups. In the first (screening group), we included all those patients referred by the Parma University Renal Transplant Center for a general oral checkup, with no specific indications for GO. The second group (non-screening group) included all those patients who specifically had been referred to the Oral Pathology and Oral Medicine Unit because of GO. We considered the following variables: gender, daily CsA dose, duration of immunosuppressive treatment, CsA plasma concentration, concomitant use of another immunosuppressive agent (azathioprine), use of other GO inducers (calcium channel blockers, anti-epileptic drugs), oral hygiene scores, and other drugs taken at the time of oral examination. Results: Fisher’s exact test and chi square test demonstrated that in the screening group, duration of immunosuppressive treatment and oral hygiene scores were associated both with the prevalence and the high GO scores (P1 DIT <0.0001; P2 DIT = 0.0023; P1 hyg = 0.0084; P2 hyg = 0.0068). In the screening group, concomitant use of CsA and azathioprine is related to a low development degree of GO (P = 0.0088). In the non-screening group, we found a significant association between poor oral hygiene and high degree of GO (P = 0.0349). Conclusion: In addition to a probable genetic predisposition, duration of immunosuppressive treatment and oral hygiene status are the most important variables related to development and degree of GO during the use of CsA in this study.