We studied 335,682 county residents, of whom 113,298 had been prescribed antihypertensive treatment (AHT), in the period 1989-2002 in North Jutland County, Denmark to examine the relation between different AHTs and the risk of renal cell carcinoma (RCC). An internal comparison was performed among the different classes of AHT users with users of beta blockers as the reference, in order to address potential confounding and bias. The average follow-up was 10 years (range 0-13). Use of any AHT was associated with RCC (relative rate (RR)=1.6, 95% confidence interval (CI) 1.3-1.9) compared with nonusers in the general population. Specific classes of AHTs were nonsignificantly associated with RCC, but compared with users of beta blockers, the numbers observed were close to expectation. Analyses by duration of follow-up and number of prescriptions revealed no clear trends for any antihypertensive agent and after 5-years of follow-up, the RRs for all classes of AHT decreased. The elevated RRs for RCC among users of AHTs compared with the general population are unlikely to be causal, but rather reflect confounding due to failure to control for pre-existing hypertension, and protopathic bias, due to the presence of hypertension as an early sign of kidney disease.