Coronary artery ligation is the standard technique to induce regional myocardial infarction in small animal models. However, opening the chest and incising the pericardium independently influence post-MI remodelling. Our purpose was to develop and characterize a novel closed chest model of regional myocardial infarction (MI) in the rabbit of increased clinical relevance. Coronary angiography was performed percutaneously in New Zealand White Rabbits (NZW) using pre-formed catheters. A 0.36 mm thrombogenic coil was positioned in the circumflex artery to induce closed chest MI. Of rabbits undergoing coil deployment 40 % survived until day 100. Rabbits were classified as small MI (n = 5), moderate MI (n = 6) and large MI (n = 6) < 15 %, 15 - 30 %, > 30 % of LV myocardial volume respectively) or sham controls (n=11). Transthoracic echocardiographic images were obtained 0, 3, 5, 7, 14, 28, 60, 100 days post procedure. At day 100, LVEDP was measured before and after plasma substitute infusion. Hearts were subsequently excised and chamber stiffness (Kc) was derived from the passive pressure-volume relationship. Cardiac weight, dimensions and MI as a percentage of LV volume (MI%) were also recorded. Differences in percentage fractional shortening (%FS) were apparent from day 14. %FS was reduced in rabbits with large and moderate MI compared to controls (day 100, p < 0.005 and p < 0.05, respectively). LVEDP was increased in large and moderate MI compared to small MI and controls (26 mmHg +/- 6 and 21 mmHg +/- 5 vs. 9 mmHg +/- 1 and 7 mmHg +/- 3 p < 0.005); these differences were maintained during plasma substitute infusion. Kc in large MI was significantly less than moderate MI, small MI or control (all p < 0.05). Direct morphometric measurements distinguished between all groups.This study provides the first description of post-infarction remodelling after coronary artery occlusion where the pericardium remains intact in a small animal model. We believe it may provide a more physiologically and clinically relevant in vivo assay system of left ventricular dysfunction after myocardial infarction.