This study aimed to compare the therapeutic effects and adverse events of the multikinase inhibitors sorafenib, sunitinib, pazopanib and axitinib in advanced renal cell carcinoma (RCC). A meta-analysis of randomized controlled trials was performed to assess the effects of multikinase inhibitors among patients with advanced RCC. The data of median progression-free survival (PFS), median overall survival (OS), progressive disease rate (PDR), objective response rate (ORR) and grade 3/4 adverse events were extracted to assess therapeutic effects and toxicity, respectively. It was found that multikinase inhibitors are more effective in extending PFS [hazard ratio (HR)=0.58; 95% confidence interval (CI): 0.45-0.74; P<0.0001), controlling tumor progression [relative risk (RR)=0.67; 95% CI: 0.55-0.83; P=0.0002) and ORR (RR=2.93; 95% CI: 1.40-6.14; P=0.004) compared with placebo or interferon-α. Patients treated with multikinase inhibitors had significantly higher rates of grade 3 or 4 hypertension (RR=6.00; 95% CI: 3.36-10.69; P<0.00001), diarrhea (RR=5.84; 95% CI: 3.06-11.16; P<0.00001), nausea (RR=2.30; 95% CI: 1.16-4.54; P=0.02), vomiting (RR=1.84; 95% CI: 1.00-3.41; P=0.05) and hand-foot skin reaction (RR=11.78; 95% CI: 5.16-26.93; P<0.00001). Multikinase inhibitors can significantly control disease progress and improve the ORR. However, they are also associated with a higher risk of grade 3 and 4 hypertension and gastrointestinal events. Proper management of these events is necessary to improve patient quality of life.