Two methods of predicting plasma procainamide concentrations (PPCs) for a sustained-release procainamide (SRP) dosage form were compared using previously published data on 12 healthy subjects. Methods A and B were both based on a one-compartment pharmacokinetic model requiring an elimination rate constant and area under the concentration-time curve from an immediate-release oral procainamide dosage form and in vitro dissolution data from the SRP product. Method A also used an absorption rate constant. The predicted versus measured PPCs for two sets of peak and trough concentrations in each subject were evaluated using linear regression. The mean predicted PPCs by both methods followed the measured PPCs closely; however, the time of peak concentration was predicted more accurately by method A. The evaluation of predictive performance showed good precision and a small but statistically significant bias with either method, peak values were overpredicted and trough values were underpredicted. These two methods adequately predicted plasma procainamide concentrations in healthy subjects following a sustained-release procainamide preparation.