This study aimed to determine whether lower values of left ventricular (LV) global work index (GWI) at baseline were associated with a reduction in LV functional recovery and poorer long-term prognosis in patients with reduced LV ejection fraction (LVEF ≤40%) following ST-segment elevation myocardial infarction (STEMI). A total of 197 individuals (62 ± 12 years, 75% male) with STEMI treated with primary percutaneous coronary intervention and reduced LVEF were evaluated. All patients were followed up for the occurrence of all-cause mortality and the presence of LVEF normalization at 6 months (LVEF ≥50%). The median LVEF was 36% (interquartile range 32-38) and the mean value of LV GWI was 1041 ± 404 mmHg% at baseline. At 6-month follow-up, 41% of patients had normalized LVEF. On multivariable logistic regression, higher values of LV GWI were independently associated with LVEF normalization at 6 months of follow-up (odds ratio 1.32 per 250 mmHg%, P = 0.038). Over a median follow-up of 112 months, 40 patients (20%) died. LV GWI <750 mmHg% was independently associated with all-cause mortality (HR 3.85, P < 0.001) and was incremental to LV global longitudinal strain (P = 0.039) and LVEF (P < 0.001). In individuals with an LVEF ≤40% following STEMI, higher values of LV GWI were associated with a greater probability of LVEF normalization at 6-month follow-up. In addition, lower values of LV GWI were independently associated with increased all-cause mortality at long-term follow-up, providing incremental prognostic value over LVEF and minor incremental prognostic value over LV global longitudinal strain.