Objective To investigate the synergistic effect of calcium channel blocker on cyclosporine-induced gingival overgrowth (GO). Methods 130 renal transplant patients treated with cyclosporine were divided into group A (with calcium channel blocker) and group B (without calcium channel blocker). Demographic, pharmacologic and periodontal data were recorded. The prevalence and severity of GO were compared between the two groups. Three calcium channel blockers, including nifedipine, amlodipine and felodipine, were administered in the patients of group A. The relationships between these three calcium channel blockers and the prevalence of GO were analyzed. Results The patients receiving calcium channel blocker showed significantly higher prevalence of GO (44/73,60 % ) than those without calcium channel blocker (22/57, 39 %) (P＜0. 05). A higher proportion of mild GO (37 %) in group A was also observed than in group B (19 %, P＜0. 05). There were no significant differences in the proportions of moderate and/or severe GO between the two groups (P＞0. 05). Periodontal variables, including plaque index and papilla bleeding index, were significantly higher in GO patients than in those without GO in both two groups (P＜0. 05). In addition, the prevalence of GO in patients receiving nifedipine (77 %) was higher than in those receiving amlodipine (57 %) or felodipine (50 %). Conclusion The combination with calcium channel blocker is a risk factor of cyclosporine-induced GO and the use of nifedipine should be avoided for these at-risk patients.