Chronic allograft nephropathy and calcineurin inhibitor toxicity may cause graft loss. Sirolimus may be considered for use in these situations. About 30% to 50% of patients on sirolimus therapy have mild or severe adverse effects. We aimed to evaluate the mild and severe adverse effects of sirolimus that limit its use. Since 1985, 1385 renal transplantation were performed at our center. Eighty-eight of these renal transplant recipients (64 male, 24 female; mean age, 35.9 ± 9.9 years (range, 21-59 years) received sirolimus for various reasons, which were included in this study. Possible adverse effects of sirolimus were evaluated during the follow-up. Each patient had a physical examination, and serum lipid levels, hemoglobin concentration, serum electrolyte levels were assessed. Five of the 88 patients showed no increase in proteinuria (5.6%), 83 patients had an increase in proteinuria. Proteinuria increased from a mean of 192 ± 316 mg/day to 449 ± 422 mg/day. Only 3 patients had heavy proteinuria (> 3 g/day), and sirolimus was discontinued because of the proteinuria. Proteinuria in the other patients was well controlled with angiotensin-converting enzyme and/or angiotensin II receptor inhibitors. After sirolimus conversion, serum cholesterol levels increased from 187 ± 42 mg/dL to 214 ± 52 mg/dL, and serum triglyceride level increased from 161 ± 61 mg/dL to 194 ± 102 mg/dL. All patients except 4 who received hypolipidemic agents responded, and serum lipid levels fell to an acceptable level. Four patients did not respond to the hypolipidemic therapy. Another 4 patients developed unilateral lower extremity edema and sirolimus was stopped. One patient had generalized arthralgia. In conclusion; sirolimus appears to have limited serious adverse effects and mild or moderate adverse effects such as hyperlipidemia and proteinuria that can be easily controlled. Because we avoid calcineurin inhibitors, it is worthwhile to convert to sirolimus in selected patients in whom calcineurin inhibitor adverse effects and toxicity are seen.