Background: It is unknown whether the existence of severe bystander damage will affect left ventricular (LV) healing following primary percutaneous coronary intervention (PPCI). The aim of the present analysis was to follow LV recovery using 2D speckle tracking echocardiography (2-D STE) in cases with single versus multiple vessel disease with acute myocardial infarction (AMI) who underwent PPCI and to assess major adverse cardiovascular events (MACEs) within 3 months. Patients and methods: This work was conducted at Assiut University Heart Hospital. Of 1026 screened subjects with AMI needing PPCI and assessed for eligibility, only 89 cases fulfilled the inclusion criteria. They were classified into Group A: single vessel and Group B: multiple vessel (≥2 vessels) disease. Their data were obtained on admittance and after 90 days. Results: In group A compared to group B, there was a statistically preferable value at baseline in the global longitudinal strain- Apical 2 chamber (GLS-A2C) (-12.05 ± 3.57 vs. -10.38 ± 3.92, P =0.039). At follow-up, the improvement was in all 2-D STE variables, including GLS-long axis (GLS-LAX) (-13.09 ± 3.84 vs.-10.75 ± 3.96, P =0.006), GLS- apical 4 chamber (GLS-A4C) (-13.23 ± 3.51 vs.-10.62 ± 4.08, P=0.002), GLS-A2C (-13.85 ± 3.41 vs-10.93 ± 3.97, P<0.001) and GLS- average (GLS-AVG, P=0.001). There was a considerable negative correlation between the recovery of LV performance and the existence of multi-vessel lesions (P=0.009). There was no variance between the groups regarding MACEs. Conclusions: Patients with single vessel lesions who underwent PPCI to the culprit lesion had better recovery of LV function than those with multi-vessel (≥2 vessels) lesions who underwent PPCI to the culprit lesion only. The presence of multivessel involvement was an independent risk factor for deterioration in GLS.