Recent adjuvant vascular endothelial growth factor tyrosine kinase inhibitor trials in resected high-risk renal cell carcinoma that compared sunitinib, sorafenib, pazopanib, and axitinib with placebo controls have demonstrated mixed impact on disease-free survival, no improvement in overall survival, and, thus, controversy. Here, we discuss the results and conduct of these trials to provide new insight into the goals and strategies of treating resected renal cell cancer that is at high risk for recurrence. The potential for leveraging what we have learned from these trials to conduct successful contemporary adjuvant and perioperative immune checkpoint inhibition trials and future adjuvant trial design is discussed.