Radio-frequency catheter ablation (RCA) is an established treatment for ventricular tachycardia (VT). A key feature of the RCA procedure is the need for a mapping approach that facilitates the identification of the target ablation site. In this study, we investigate the effect of the location of the reference potential and spatial anatomical constraints on the accuracy of an algorithm to identify the target site for ablation therapy of VT. This algorithm involves processing body surface potentials using the single equivalent moving dipole (SEMD) model embedded in an infinite homogeneous volume conductor to model cardiac electrical activity. We employed a swine animal model and an electrode array of nine electrodes that was sutured on the epicardial surface of the right ventricle. We identified two potential reference electrode locations: at an electrode most far away from the heart (R1) and at the average of all 64 body surface electrode potentials (R2). Also, we developed three spatial "constraining" schemes of the algorithm used to obtain the SEMD location: one that does not impose any constraint on the inverse solution (S1), one that constrains the solution into a volume that corresponds to the heart (S2), and one that constrains the solution into a volume that corresponds to the body surface (S3). We have found that R2S1 is the most accurate approach (p < 0.05 versus R1S1 at earliest activation time-EAT) for localizing epicardial electrical sources of known locations in vivo. Although the homogeneous volume conductor introduces systematic error in the estimated compared to the true dipole location, we have observed that the overall error of the estimated interelectrode distance compared to the true one was 0.4 ± 0.4 cm and 0.4 ± 0.1 cm for the R1S1 and R2S1 combinations, respectively, at the EAT (p = N.S.) and 1.0 ± 0.6 and 0.5 ± 0.4 cm, respectively, at the pacing spike time (PST, ). In conclusion, our algorithm to estimate the SEMD parameters from body surface potentials can potentially be a useful method to rapidly and accurately guide the catheter tip to the target site during a RCA procedure without the need for spatial anatomical information obtained by conventional imaging modalities.