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The objective of this study was to investigate the replacement of alfalfa clover by blue panic grass (Panicum antidotale) as a sub-tropical browse in Saudi Arabia on rumen fermentation characteristics, methane emission and productivity of dairy cows in late lactation. Two experiments were conducted, the first experiment was in vitro assay using semi-automatic system of gas production to compare the ruminal fermentation pattern and methane emission of alfalfa clover and blue panic grass, while the second experiment was tested the complete replacement of alfalfa clover by blue panic grass on dry matter intake, milk yield and composition in dairy cows. The results of the first experiment revealed that there are wide variations in crude protein (CP) content of alfalfa clover (20.3%) and blue panic grass (8.4%). The neutral detergent fiber (NDF) was higher in blue panic grass (62.3%) than in alfalfa clover (51.0%). The secondary compound analysis showed higher contents of blue panic grass than alfalfa clover of total phenol (TP; 27 vs. 11 eq-g tannic acid/kg DM), total tannins (TT, 17 vs. 3.6 eq-g tannic acid/kg DM) and condensed tannins (CT, 2.6 vs. 0.5 eq-g leucocyanidin/kg DM). The cumulative gas production at 24 h was higher (P<0.05) for alfalfa clover than blue panic grass. The results of methane emission showed a decline (P<0.05) in methane emission in blue panic grass compared with alfalfa clover. There were no significant differences between alfalfa clover and blue panic grass in rumen pH, NH3-N concentration and protozoa number. The true degradation of organic matter (TDOM), short chain fatty acids (SCFA) and partitioning factor (PF) were lower in blue panic grass than in alfalfa clover. The results of the second experiment revealed that the group of lactating dairy cows fed blue panic grass produced less (P<0.05) milk yield (6.74 vs. 5.44 kg/d) and fat corrected milk (5.58 vs. 4.62 kg/d) than alfalfa clover group. Blue panic grass group revealed that milk fat was higher than in alfalfa group, while milk protein, lactose, non-fat solid (SNF) and ash percentages had no differences between two groups. Blood metabolite measurements showed that dairy cows fed blue panic grass had lower (P>0.05) total protein, globulin, glucose, urea and cholesterol compared to alfalfa group except creatinine, which was higher (P>0.05) in blue panic grass group. It can be concluded that although blue panic grass reduced methane emission in vitro, complete replacement of blue panic grass instead of alfalfa clover affects negatively on the productivity of lactating dairy cows in semi-arid regions.