Post-operative atrial fibrillation is a complication with high morbidity. In patients on prior-to-admission beta-blockers, early post-operative beta-blockade reduces atrial fibrillation risk; however, this benefit is not studied in hemodynamically unstable patients requiring vasopressors. A retrospective analysis was performed at two high-volume centers of adult patients on home beta-blockers, undergoing non-cardiac surgery between 2005 and 2015, and who required post-operative vasopressors. Patients were divided into early beta-blockers (within 24h) or delayed from vasopressor cessation. The primary outcome was the atrial fibrillation incidence. A propensity score was developed for early beta-blockers and used for adjustment. Eight-hundred seventy one patients required post-operative vasopressors; 423 in the early group and 448 in the delayed group. In the delayed beta-blocker group, intraoperative hypotension was more common (21.6% versus 24.1%, p<0.001), APACHE III scores higher (56.6 versus 50.8, p<0.001) and more post-operative norephinephrine use (56.7% veruss 30.3%, p<0.001). Eighty eight patients developed atrial fibrillation: 40 in the early group, and 48 in the delayed group (p=0.538). After adjustment, early beta-blockade was not associated with changed incidence of atrial fibrillation. In patients requiring postoperative vasopressors, early beta-blockade did not protect against postoperative atrial fibrillation.