S-allylcysteine (SAC) is an organosulphur-containing compound derived from garlic. Studies have shown that garlic is beneficial in the treatment of cardiovascular diseases. This study aims to elucidate if SAC is responsible for this cardioprotection using acute myocardial infarction (AMI) rat models. In addition, we hypothesized that SAC may mediate cardioprotection via a H₂S-related pathway. Rats were pretreated with saline, SAC (50mg/kg/day), SAC+ propagylglycine (PAG) (50mg + 10mg/kg /day) or PAG (10mg/kg/day), for seven days prior to AMI induction and sacrificed 48hr after. Our results showed that SAC significantly lowered mortality (12.5% vs. 33.3%, p<0.05) and reduced infarct size. SAC+PAG and PAG-treated rats had larger infarct sizes than controls (60.9± 0.01% and 62.0±0.03% respectively vs. 50.0±0.03%; p<0.05). Pretreatment with SAC did not affect blood pressure, but blood pressure was significantly elevated in SAC+PAG and PAG-treated groups (p<0.05). In addition, plasma H₂S levels and left ventricular cystathionine--lyase (CSE) activities were analysed to investigate the involvement of H₂S. CSE is the enzyme responsible for H₂S production in the heart. SAC increased left ventricular CSE activity in AMI rats (2.75±0.34 µmol/g protein/hr vs. 1.23±0.16 µmol/g protein/hr; p<0.01). SAC+PAG treated rats had significantly lower CSE activity compared to SAC-treated group (1.22±0.27µmol/g protein/hr vs. 2.75±0.34µmol/g protein/hr; p<0.05). Similarly, SAC-treated rats had higher plasma H₂S concentration when compared to controls and SAC+PAG-treated group. Protein expression studies revealed that SAC upregulated CSE expression (1.1 fold of control; p<0.05) whereas SAC+PAG and PAG downregulated its expression (0.88 fold of control in both groups; p<0.005). In conclusion, our study provides novel evidence that SAC is protective in myocardial infarction via a H₂S-related pathway.