Purpose. The impact of patient-specific factors on the choice of β-blocker versus calcium channel blocker therapy for rate control in emergency department (ED) patients treated for atrial fibrillation (AF) was investigated. Methods. A retrospective cohort study was conducted to evaluate the influence of demographics, prior medication use, hemodynamic and clinical characteristics, and other variables on selection of first-line therapy for AF among patients admitted to the ED of an academic medical center over a 22-month period (October 2012-July 2014) who received i.v. treatment with either the β-blocker metoprolol (n = 45) or the calcium channel blocker diltiazem (n = 55) for rate control. Results. Significant predictors of the selection of metoprolol versus diltiazem included a past history of AF (odds ratio [OR], 8.3; 95% confidence interval [CI], 1.396-72.713; p = 0.032) or diabetes mellitus (OR, 7.2; 95% CI, 1.208-58.490; p = 0.042) and being prescribed a β-blocker prior to presentation (OR, 27.8; 95% CI, 4.704-272.894; p = 0.001); a history of calcium channel blocker use prior to ED presentation was a negative predictor of β-blocker use for initial rate control (OR, 0.1; 95% CI, 0.005-0.265; p = 0.002). No differences in the effectiveness or safety of diltiazem and metoprolol were identified. Indicators of hemodynamic and clinical response to ED management were not predictive of discharge medication selection. Conclusion. The drug class used for rate control prior to ED admission was the most significant predictor of medication selection for rate control in the ED setting.