Objective: Immunosuppressive drugs may induce an increase of the gingival connective tissue in the extracellular matrix. The aim of this study was to assess the effectiveness of nonsurgical periodontal treatment in reducing gingival overgrowth (GO) in transplant patients taking cyclosporin A (CsA) or tacrolimus (Tcr). Method and Materials: An observational cohort study employing 68 transplant patients with diagnosis of GO, 51 taking CsA and 17 in therapy with Tcr, was performed at the Periodontal Unit of the School of Dental Sciences (University of Trieste, Italy). Percentages of plaque index (PI), bleeding on probing (BoP), sites with probing depth (PD) > 3 mm, and hypertrophy index (HI) were registered at baseline, 90 days, 180 days, and at 1 year after nonsurgical periodontal therapy. Furthermore, HI at baseline and after 1 year was investigated by multiple linear regression. Results: Both groups have significantly improved their clinical parameters: CsA group: PIbaseline = 41.67%; PIyear = 33%; BoPbaseline = 13.88%; BoPyear = 6.94%; PD > 3 mmbaseline = 18.6%; PD > 3 mmyear = 12.96%; HIbaseline = 22%; HIyear = 10%; Tcr group: PIbaseline = 40.73%; PIyear = 38.54%; BoPbaseline = 20.78%; BoPyear = 12.5%; PD > 3 mmbaseline = 21.53%; PD > 3 mmyear = 13.19%; HIbaseline = 12%; HIyear = 6.5%. Age showed a statistical negative correlation with HI at baseline (P .05), while PD > 3 mm was positively correlated to the baseline HI (P .001). Only HI at baseline showed a statistically significant negative relation with HI at 1 year (P .001). Conclusion: After nonsurgical periodontal therapy no patients needed additional periodontal surgery. Nonsurgical periodontal treatment itself represents an efficacious therapy in transplant patients treated with CsA and Tcr. Keywords: cyclosporin A, gingival overgrowth, organ transplant, periodontitis, tacrolimus