Earlier studies indicate an inverse relationship between hospital volume and mortality after primary angioplasty for patients presenting with ST-segment elevation myocardial infarction (STEMI). However, contemporary data are lacking. To assess the relationship between hospital primary angioplasty volume and outcomes and quality of care measures in patients presenting with STEMI. An observational analysis of data on 29,513 patients presenting with STEMI and undergoing primary angioplasty in the American Heart Association's Get With the Guidelines registry. Patients were treated between July 5, 2001, and December 31, 2007, at 166 angioplasty-capable hospitals across the United States. Hospitals were divided into tertiles (<36 procedures per year, 36-70 procedures per year, and >70 procedures per year) based on their annual primary angioplasty volume. Door-to-balloon (DTB) times, length of hospital stay, adherence with evidence-based quality of care measures, and in-hospital mortality. Compared with low- and medium-volume centers, high-volume centers had better median DTB times (98 vs 90 vs 88 minutes, respectively; P for trend < .001). High-volume centers were more likely than low-volume centers to follow evidence-based guidelines at discharge. Length of stay was similar between the 3 groups (P for trend = .13). There was no significant difference in the crude mortality between the tertiles of volume (incidence rate, 3.9% vs 3.2% vs 3.0% for low-, medium-, and high-volume centers, respectively; P = .26 and P = .99 for low- and medium- vs high-volume hospitals, respectively). Sequential multivariable modeling using generalized estimating equations revealed no significant association between hospital primary angioplasty volume and in-hospital mortality (adjusted odds ratio [OR], 1.22; 95% confidence interval [CI], 0.78-1.91; P = .38 and adjusted OR, 1.14; 95% CI, 0.78-1.66; P = .49 for low- and medium- vs high-volume hospitals, respectively). In a contemporary registry of patients with STEMI, higher-volume primary angioplasty centers vs lower-volume centers were associated with shorter DTB times and more use of evidence-based therapies, but not with adjusted in-hospital mortality or length of hospital stay.