Enhancing the understanding of the fate of wastewater-derived organic micropollutants in rivers is crucialto improve risk assessment, regulatory decision making and river management. Hyporheic exchange andsediment bacterial diversity are two factors gaining increasing importance as drivers for micropollutantdegradation, but are complex to study infield experiments and usually ignored in laboratory tests aimedto estimate environmental half-lives. Flume mesocosms are useful to investigate micropollutantdegradation processes, bridging the gap between thefield and batch experiments. However, few studieshave usedflumes in this context. We present a novel experimental setup using 20 recirculatingflumesand a response surface model to study the influence of hyporheic exchange and sediment bacterialdiversity on half-lives of the anti-epileptic drug carbamazepine (CBZ) and the artificial sweeteneracesulfame (ACS). The effect of bedform-induced hyporheic exchange was tested by three treatmentlevels differing in number of bedforms (0, 3 and 6). Three levels of sediment bacterial diversity wereobtained by diluting sediment from the River Erpe in Berlin, Germany, with sand (1 : 10, 1 : 1000 and1 : 100 000). Our results show that ACS half-lives were significantly influenced by sediment dilution andnumber of bedforms. Half-lives of CBZ were higher than ACS, and were significantly affected only by thesediment dilution variable, and thus by bacterial diversity. Our results show that (1) theflume-setup isa useful tool to study the fate of micropollutants in rivers, and that (2) higher hyporheic exchange andbacterial diversity in the sediment can increase the degradation of micropollutants in rivers.