Fatigue is the most common symptom associated with cancer and cancer treatment. We performed an up-to-date meta-analysis to determine the incidence and relative risk of fatigue in patients (pts) with cancer treated with sorafenib (SO), sunitinib (SU) and pazopanib (PZ). PubMed databases were searched for articles published till August 2013. Eligible studies were selected according to PRISMA statement. Summary incidence, relative risk (RR), and 95% CIs were calculated using random-effects or fixed-effects models based on the heterogeneity of selected studies. Fifteen studies were included in this analysis. A total of 6996 pts was enrolled: 2260 had renal cell carcinomas (RCC), 1691 non-small cell lung cancers, 1290 breast cancers, 823 hepatocellular carcinomas, 362 soft tissue sarcomas, 304 gastrointestinal solid tumors, 165 neuroendocrine tumors and 101 melanomas. When stratified by drug, SO registered lower incidence and RR of all and high-grade fatigue as compared to SU, whereas the difference between SO and PZ was significant only for all-grade fatigue (p< 0.001). The difference between SU and PZ was significant for high-grade (p< 0.001) but not for all-grade fatigue (p=0.52). In RCC patients, PZ showed the lower incidence and RR of all and high-grade fatigue. The differences were significant for SU vs. SO (p<0.001), SU vs. PZ (p< 0.001) and SO vs. PZ (p< 0.001). Treatment with SO, SU and PZ is associated with an increased incidence of fatigue in pts with cancer. Early and appropriate management is required in order to avoid unnecessary dose reductions and transitory or definitive treatment discontinuations. © 2014 Wiley Periodicals, Inc.