The objective of this study was to evaluate the effect of replacing corn silage with cactus cladodes (Opuntia stricta (Haw.) Haw) plus sugarcane bagasse and urea in diets with similar neutral detergent fiber (NDF) contents on potentially digestible dry matter intake (pdDM), ruminal fermentation, nitrogen utilization efficiency, and microbial protein synthesis in sheep. Five substitution levels (0, 175, 350, 525, and 700 g/kg DM) were tested as experimental treatments, using five rumen-fistulated sheep (average body weight of 37.5 +/- 5.57 kg) distributed in a 5 & times; 5 Latin square design. The intake of pdDM decreased linearly with increasing levels of substitution (P < 0.01). Ruminal pH was not affected by the replacement (6.2 +/- 0.04). Ruminal ammonia nitrogen (NH3-N) increased linearly with increasing substitution levels (15.10-19.08 mg/dL; P = 0.034). Additionally, a significant interaction between substitution levels and collection time was observed, with higher NH3-N peaks as the replacement level increased (19.00-27.12 mg/dL; P < 0.001). Conversely, nitrogen intake (P = 0.048), fecal nitrogen (P = 0.022), retained nitrogen (g/day, P = 0.039; % of intake, P = 0.034), and microbial protein synthesis (P = 0.006) decreased with increasing substitution levels. In contrast, urinary nitrogen as a percentage of intake and blood urea nitrogen increased linearly. Under the experimental conditions evaluated in this study, replacing corn silage with the tested integrated roughage strategy formulated solely based on total NDF concentration reduced fermentable energy availability, nitrogen use efficiency, and microbial protein synthesis.