Background & aims: An oral [13C]urea protocol may provide a simple method for measurement of urea production. The validity of single pool calculations in relation to a reduced sampling protocol was assessed. Methods: In eight fed and five fasted piglets, plasma urea enrichments from a 10 h sampling protocol were measured following an intragastric [13C]urea bolus. Blood [13C]bicarbonate was measured to trace gut [13C]urea oxidation. Two-compartment and regression (single pool) computations were performed. Pool sizes were compared to urea distribution over total body water (TBW). Shorter protocol duration was tested in regression simulations. Results: Differences in urea kinetics between fed and fasted piglets did not reach statistical significance. Mean (±SE) urea pool from TBW times plasma urea concentration was 2.2±0.16 mmol kg−1. Two-compartment modelling yielded similar results for pool size (despite the oxidation of a small amount of urea tracer). Urea appearance rate was 306±18 μmol kg−1 h−1. Regression calculations overestimated urea appearance rate vs. compartmental model (). When samples <2 h were discarded, results were comparable to compartmental calculations even if protocol length was 6 h (325±24 μmol kg−1 h−1, NS). Conclusions: Regression calculations using plasma enrichments sampled between 2 and 6 h after oral [13C]urea administration provide accurate rates of urea production, and are not affected by tracer oxidation.