Aims: To elucidate how granular sludge inoculum and particle-rich organic loading affect the structure of the microbial communities and process performance in upflow anaerobic sludge bed (UASB) reactors. Methods and Results: We investigated four reactors run on dairy manure filtrate and four on pig manure supernatant for three months achieving similar methane yields. The reactors fed with less particle rich pig manure stabilized faster and had highest capacity. Microbial community dynamics analysed by a PCR/denaturing gradient gel electrophoresis approach showed that influent was a major determinant for the composition of the reactor communities. Comparisons of pre- and non-adapted inoculum in the reactors run on pig manure supernatant showed that the community structure of the nonadapted inoculum adapted in approximately two months. Microbiota variance partitioning analysis revealed that running time, organic loading rate and inoculum together explained 26 and 31% of the variance in bacterial and archaeal communities respectively. Conclusions: The microbial communities of UASBs adapted to the reactor conditions in treatment of particle rich manure fractions, obtaining high capacity, especially on pig manure supernatant. Significance and Impact of the Study: These findings provide relevant insight into the microbial community dynamics in startup and operation of sludge bed reactors for methane production from slurry fractions, a major potential source of biogas.