Background: Circulating cell-free DNA (cfDNA) mostly originates from tumors and its level correlates with treatment. We assessed whether the level of plasma cfDNA could help monitor recurrence after nephrectomy. Methods: This study included 92 patients with clear cell renal cell carcinoma (cRCC). Quantitative real-time PCR was used to measure the level of plasma cfDNA before and after nephrectomy. Results: The pretreatment level of plasma cfDNA in patients with metastatic cRCC (6.04 ± 0.72) was significantly higher than in those with localized cRCC (5.29 ± 0.53, p = 0.017) or controls (0.65 ± 0.29, p < 0.001). Of patients with localized cRCC, those with recurrence had a significantly higher plasma cfDNA level than those without (p = 0.024). The patients with a high plasma cfDNA level had a significantly higher recurrence rate than those with a low plasma cfDNA level before and after nephrectomy (p = 0.018). Conclusion: The level of plasma cfDNA may be useful as a tool to monitor patients during follow-up and guide further diagnostic work-up for the detection of recurrence.