Background: Examine 90-day postoperative mortality and its predictors following shoulder arthroplasty. Methods. We identified vital status of all adults who underwent primary shoulder arthroplasty (Total shoulder arthroplasty (TSA) or humeral head replacement (HHR)) at the Mayo Clinic from 1976-2008, using the prospectively collected information from Total Joint Registry. We used univariate logistic regression models to assess the association of gender, age, body mass index, American Society of Anesthesiologist (ASA) class, Deyo-Charlson comorbidity index, an underlying diagnosis and implant fixation with odds of 90-day mortality after TSA or HHR. Multivariable models additionally adjusted for the type of surgery (TSA versus HHR). Adjusted Odds ratio (OR) with 95% confidence interval (CI) were calculated. Results: Twenty-eight of the 3, 480 patient operated died within 90-days of shoulder arthroplasty (0.8%). In multivariable-adjusted analyses, the following factors were associated with significantly higher odds of 90-day mortality: higher Deyo-Charlson index (OR, 1.54; 95% CI:1.39, 1.70; p < 0.001); a diagnosis of tumor (OR, 16.2; 95%CI:7.1, 36.7); and ASA class III (OR, 3.57; 95% CI:1.29, 9.91; p = 0.01) or class IV (OR, 13.4; 95% CI:2.44, 73.86; p = 0.003). BMI 30 was associated with lower risk of 90-day mortality (OR, 0.25; 95% CI:0.08, 0.78). In univariate analyses, patients undergoing TSA had significantly lower 90-day mortality of 0.4% (8/2, 580) compared to 1% in HHR (20/1, 411) (odds ratio, 0.22 (95% CI: 0.10, 0.50); p = 0.0003). Conclusions: 90-day mortality following shoulder arthroplasty was low. An underlying diagnosis of tumor, higher comorbidity and higher ASA class were risk factors for higher 90-day mortality, while higher BMI was protective. Pre-operative comorbidity management may impact 90-day mortality following shoulder arthroplasty. A higher unadjusted mortality in patients undergoing TSA versus HHR may indicate the underlying differences in patients undergoing these procedures. © 2011 Singh et al; licensee BioMed Central Ltd.