The impact of tobacco use on readmission and medical and surgical complications has been documented in hip and knee arthroplasty. However, there remains little information about the effect of smoking on the outcome after total shoulder arthroplasty (TSA). We hypothesized that active smokers are at an increased risk of poor medical and surgial outcomes after TSA. Data for patients who underwent arthroplasty of the shoulder in the USA between January 2011 and December 2015 were obtained from the National Readmission Database, and 90-day readmissions and complications were documented using validated coding methods. Multivariate regression analysis was performed to quantify the risk of smoking on the outcome after TSA, while controlling for patient demographics, comorbidities, and hospital-level confounding factors. A total of 196,325 non-smokers (93.1%) and 14,461 smokers (6.9%) underwent TSA during the five-year study period. Smokers had significantly increased rates of 30- and 90-day readmission (p = 0.025 and 0.001, respectively), revision within 90 days (p < 0.001), infection (p < 0.001), wound complications (p < 0.001), and instability of the prosthesis (p < 0.001). They were also at significantly greater risk of suffering from pneumonia (p < 0.001), sepsis (p = 0.001), and myocardial infarction (p < 0.001), postoperatively. Smokers have an increased risk of readmission and medical and surgical complications after TSA. These risks are similar to those found for smokers after hip and knee arthroplasty. Many surgeons choose to avoid these elective procedures in patients who smoke. The increased risks should be considered when counselling patients who smoke before undertaking TSA.