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Poor R-wave progression (PRWP) is a common electrocardiographic phenomenon in which the anticipated increase in R-wave amplitude in successive precordial leads, V1 to V5, fails to occur. PRWP is prevalent in approximately 10% of hospitalized adult patients, predominantly in those with coronary artery disease. Debate is ongoing on its association with myocardial infarction (MI). However, studies that showed no association failed to appraise the significance of the QRS axis in relation to PRWP among such patients with MI. In our retrospective study, we consecutively identified 150 unselected adult patients with PRWP among 660 successive admissions to the general medical floors of a tertiary care teaching hospital (Saint Vincent Hospital, Worcester, Massachusetts). After excluding patients with anterior wall Q-wave MI (defined as the presence of a QS complex or Q-wave ≥1 mm deep in V2 or V3), sudden unexpected death, MI after percutaneous coronary interventions or coronary artery bypass grafting during this hospitalization, Wolff-Parkinson-White syndrome, pacemakers, bundle branch blocks, and electrocardiograms that were of poor quality or affected by severe motion artifact, inconsistencies with patient identification, or errors in lead placement, 137 patients remained. The patients were then screened for non–ST-segment elevation MI (NSTEMI) during the present admission. The DePace criteria for PRWP were systematically used for all patients, and the QRS axis was calculated using limb leads based on Einthoven''s equilateral triangle (normal was considered −30° to 100°). Of the 137 study patients screened with PRWP, 38 had NSTEMI (25.3%). Thirty-one had a normal QRS axis (mean age ± standard deviation 71.3 ± 12 years), and 7 showed either right or left axis deviation (mean age ± standard deviation 64.3 ± 15 years). This proved to be statistically significant (p <0.0001) within this cohort of NSTEMI patients. In conclusion, PRWP determined using the DePace criteria in the presence of a normal QRS axis appears to be more significantly associated with the presence of overall MI within this cohort of NSTEMI patients. [Copyright &y& Elsevier]