The aim of this study was to evaluate the effects of increasing concentrations of three pure statins on in vitro methane production and rumen fermentation. The effects of atorvastatin, rosuvastatin and simvastatin at three concentrations (1, 10, and 100 mg/L of culture fluid) were evaluated using in vitro 24 h batch incubation of buffered rumen fluid with a 70:30 forage:concentrate substrate. All statins tested demonstrated the ability to reduce methanogenesis. Methane inhibition potential was decreasing in the following order: simvastatin > atorvastatin > rosuvastatin. Methane production was reduced (p < 0.05) by simvastatin at 10 mg/L (by 9.3%) and by atorvastatin at 100 mg/L (by 13.2%) without compromising fermentation and feed digestibility. Simvastatin at 100 mg/L decreased methane production by 26.2%, however, net production of volatile fatty acids (nVFA) was also reduced (p < 0.05). The only effect of rosuvastatin was a slight reduction (p < 0.05) of methane proportion at 10 and 100 mg/L. Simvastatin and atorvastatin at 100 mg/L increased (p < 0.05) relative proportion of propionate at the expense of acetate and butyrate. Ammonia-N concentrations were not affected (p > 0.05) by statins. The current study demonstrated that selected statins could selectively decrease methane production. The effects of statins on methanogenesis and overall rumen fermentation vary depending on statin type and concentration. Hydrophobic statins, such as simvastatin and atorvastatin, seem to be more effective compared to the hydrophilic statins, such as rosuvastatin.