A number of mouse models to study cardiovascular diseases have been developed over the last 10 years. Although the mouse has many favourable characteristics, its small size makes surgical procedures technically difficult. Heart failure surgery is classically achieved by ligation of the left anterior descending artery (LAD), however it is technically demanding and can have mortality rates as high as 70%^1-4. Also the degree of the injury can vary depending on the degree of collateral blood supply of each animal. We have developed a method of cryo-injury to the heart via a trans diaphragmatic approach. It is a procedure that is quickly mastered, produces reproducible results and has very little in the way of complications. Adult female C57BL/6 (n=18) (weight 20-30 grams) were used. Briefly, animals were anaesthetised and secured to a heated operating table. Myocardial infarction surgery was performed by applying a steel cryo-probe (2mm diameter) cooled in liquid nitrogen to the inferior surface to the heart through the diaphragm via an upper abdominal incision. Animals were randomised to 3 study groups: 20 second, 40 second and a 60 second cryo-injury group (n=6 per group). Animals were recovered for 6 weeks during which time, weekly weight and blood pressure (tail cuff) were measured. After 6 weeks all hearts were harvested for histology and assessed infarct size. There was no mortality for the duration of the study. Post operative tail cuff blood pressure and weights were measured in all animals. There were no significant differences between the groups. Hearts were embedded and sectioned 100μm apart, and stained with haematoxylin and eosin. Infarct size was calculated as a percentage of total ventricular volume. Infarcts were confirmed in all (100%) of hearts. Infarct size was 5.01% +/- 0.31%, 9.18% +/- 0.257%, 12.35% +/- 0.295% (mean +/- SEM) for 20, 40, 60 second cryo-injury respectively, p<0.001 (20s v 60s, 20s v 40s, 40s v 60s). Cryo-injury has been shown to be effective in producing myocardial infarction in mice. It has been shown to produce a reproducible injury whose size can be varied by applying the cryo-probe on the heart surface for different periods of time. The procedure has minimal mortality and complications and could be an alternative to LAD ligation in mice.