This study was conducted to examine the influence of varying dietary cation anion difference (DCAD) on nutrient intake, digestibility, ruminal characteristics, blood acid base status and in situ digestion kinetics in Nili Ravi buffalo bulls. Four iso-nitrogenous and iso-caloric diets having -110, +110, +220 and +330 mEq/kg dry matter (DM) DCAD were formulated which were represented by A (anionic), LC (low cationic), MC (medium cationic) and HC (high cationic), respectively. These diets were used in four ruminally cannulated Nili Ravi buffalo bulls in a 4 × 4 Latin Square Design. Improved nutrient intake was recorded at high DCAD levels while digestibility remained unaffected. Ruminal ammonia nitrogen, rumen pH, acetate and acetate : propionate ratio were higher in buffalo bulls fed MC and HC diets than those fed A and LC diets. Blood pH and HCO₃⁻ also tended to increase as DCAD level was increased in the diet. Serum Ca and Cl concentrations were higher in bulls fed A and LC diets whereas serum Mg, P and S remained unaffected. Urine pH increased with increasing DCAD level. Nitrogen intake and blood urea nitrogen concentrations were also higher in bulls fed MC and HC diets. There was a consistent increase in ruminal DM and neutral detergent fiber degradability, rate of disappearance and extent of digestion at high DCAD levels in the diet. However, lag time decreased at high DCAD level. This study indicated that buffalo bulls fed MC and HC diets improved feed intake, ruminal characteristics and digestion kinetics.