Several attempts have been made to quantify microbial protein flow from the rumen; however, few studies have evaluated tradeoffs between empirical equations (microbial N as a function of diet composition) and more mechanistic equations (microbial N as a function of ruminal carbohydrate digestibility). Although more mechanistic approaches have been touted because they represent more of the biology and thus might behave more appropriately in extreme scenarios, their precision is difficult to evaluate. The objective of this study was to derive equations describing starch, neutral detergent fiber (NDF), and organic matter total-tract and ruminal digestibilities; use these equations as inputs to equations predicting microbial N (MicN) production; and evaluate the implications of the different calculation methods in terms of their precision and accuracy. Models were evaluated based on root estimated variance σˆe and concordance correlation coefficients (CCC). Ruminal digestibility of NDF was positively associated with DMI and concentrations of NDF and CP and was negatively associated with concentration of starch and the ratio of acid detergent fiber to NDF (CCC=0.946). Apparent ruminal starch digestibility was increased by omasal sampling (compared with duodenal sampling), was positively associated with forage NDF and starch concentrations, and was negatively associated with wet forage DMI and total dietary DMI (CCC=0.908). Models were further evaluated by calculating fit statistics from a common data set, using stochastic simulation, and extreme scenario testing. In the stochastic simulation, variance in input variables were drawn from a multi-variate random normal distribution reflective of input measurement errors and predicting MicN while accounting for the measurement errors. Extreme scenario testing evaluated each MicN model against a data subset. When compared against an identical data set, predicting MicN empirically had the lowest prediction error, though differences were slight (σˆe 23.3% vs. 23.7 or 24.3%), and highest concordance (0.52 vs. 0.48 or 0.44) of any approach. Minimal differences were observed between empirical MicN prediction (σˆe 25.3%; CCC 0.530) and MicN prediction (σˆe 25.3%; CCC 0.532) from rumen carbohydrate digestibility in the stochastic analysis or extreme scenario testing. Despite the hypothesized benefits of a more mechanistic prediction approach, few differences between the calculation approaches were identified.