Purpose: The aim of this study was to investigate the association of simple renal cysts (SRC) and their characteristics with renal dysfunction in a Taiwanese population. Methods: We enrolled 7,339 eligible subjects undergoing a health checkup in National Cheng Kung University Hospital between January 2001 and October 2007. Estimated glomerular filtration rate (eGFR) was calculated by the abbreviated Modification of Diet in Renal Diseases (MDRD) equation and proteinuria was determined by dipstick urinalysis. SRC were identified on the basis of standard sonographic parameters. Renal cyst characteristics, including cyst number, distribution, and size, were further investigated. Analysis of covariance and multivariate logistic regression were performed for analyses of eGFR and proteinuria, respectively. Results: Overall, 693 subjects (9.4%) had at least one SRC. Subjects with SRC had lower eGFR compared to those without SRC. Multiple cysts, not solitary ones, were associated with lower eGFR when compared to no cysts. Compared to subjects with bilateral cysts, those with unilateral cyst(s) or no cysts had higher eGFR. Subjects with cyst size ≥2 cm, but not <2cm, had lower eGFR compared to those without SRC. Subjects with multiple cysts, not solitary ones, had a higher risk of proteinuria than those without; while bilateral cysts, and not unilateral ones, increased the risk of proteinuria. Conclusion: SRC with multiple, bilateral and large-sized ( ≥2 cm) characteristics were associated with deceased eGFR; while the risk of proteinuria increased only in multiple or bilateral cysts. Subjects with SRC should also be assessed for the possibility of renal dysfunction.