OBJECTIVE To determine the impact of replacement fluid infusion site on filter life and azotemic control during continuous veno-venous hemofiltration (CVVH). METHODS Pre-dilution CVVH was conducted from February 2001 to December 2001 and then practice was changed to post-dilution (from January 2002 to July 2002). Filter life was prospectively observed and the following data obtained for each filter: starting date and time, ending date and time, heparin use, heparin dose and protamine use. Daily creatinine, urea, INR, APTT and platelet count were also collected. RESULTS Forty-eight patients were studied (33 in pre-dilution and 15 in post-dilution) for a total of 309 filters (202 in pre-dilution and 107 in post-dilution). The median filter life was significantly shorter in the post-dilution period (18.0 vs. 13.0 h, p = 0.021). Multivariate linear regression analysis showed that pre-dilution was a significant independent predictor of increased filter life (p = 0.029), together with platelet count (p = 0.0035) and heparin dose (p = 0.046). There was no significant improvement in daily creatinine and/or urea reduction in the post-dilution period (% Delta creatinine: 7.9 vs. 10.2%/day, p = 0.99, urea: 5.4 vs. 9.7%/ day, p = 0.78). CONCLUSIONS Post-dilution was associated with reduced filter life without any beneficial effect on daily changes in urea and creatinine levels. Pre-dilution appears a preferable technical approach to CVVH.