Abstract BACKGROUND AND AIMS When polymethyl methacrylate (PMMA) membranes are used in renal replacement therapy, inflammatory cytokines and other substances are removed by adsorption. However, these filters are also prone to clogging and the filter lifetimes are likely to be short. In the present study, we investigated the effects of the hollow fiber inner diameter and membrane area of PMMA membranes on the filter lifetime and protein removal performance using an in vitro continuous hemofiltration (CHF) experimental model with porcine blood. METHOD Three filters with different hollow fiber inner diameters and membrane areas were used: CH-1.0N (membrane area, 1.0 m2; hollow fiber inner diameter, 200 µm), CH-1.0W (prototype: 1.0 m2; 240 µm), and CH-1.8W (1.8 m2; 240 µm). Blood samples from one pig were divided into three portions, and in vitro CHF experiments for each filter were performed at QB = 100 mL/min and QS = QF = 10 mL/min. The pressure changes, total protein concentration in the blood, and total protein amount in the filtrate were measured during the experiments. From the results of the pressure changes, the time for the TMP to reach 200 mmHg (corresponding to the time when the membrane pores were clogged) and the time for the pressure drop through the filter to reach 200 mmHg (corresponding to the time when the hollow fibers were clogged) were calculated as the filter lifetime for comparative evaluation. RESULTS The time for the TMP to reach 200 mmHg was significantly longer with CH-1.8W than that with CH-1.0N or CH-1.0W (Friedman test, P < .05, n = 15). The time for the pressure drop through the filter to reach 200 mmHg was significantly longer with CH-1.8W than that with CH-1.0N or CH-1.0W (Friedman test, P < 0.05, n = 15). The results suggest that an increased membrane surface area is an essential factor for extending the filter lifetime. The total protein adsorption was significantly higher for the CH-1.0W and CH-1.8W filters than for the CH-1.0N filter (two-way ANOVA and post hoc Tukey test, P < 0.01, n = 15). Thus, the membranes with larger hollow fiber inner diameters (CH-1.8W and CH-1.0W) adsorbed more protein. CONCLUSION A larger membrane area contributes to a longer filter lifetime, whereas increase in the hollow fiber inner diameter does not. On the other hand, the protein removal performance, especially the adsorption performance, was higher for membranes with larger hollow fiber inner diameters.