Background Predictors of asthma exacerbations, poor asthma control, or extreme β-agonist overuse may be of clinical utility in the management of asthma. Objective To investigate characteristics that predict subsequent adverse outcomes in asthma. Methods An independent 24-week, randomized controlled trial of 303 adult patients with asthma who are at risk, which compared the efficacy of SMART (single budesonide-formoterol inhaler as maintenance and reliever therapy) with a fixed-dose regimen with salbutamol as reliever (“Standard”). Inhaled medication use was measured by electronic monitoring. Baseline characteristics that were predictors of subsequent severe asthma exacerbations, poor asthma control (Asthma Control Questionnaire –5 score ≥1.5), and “extreme” β-agonist overuse (>16 budesonide-formoterol actuations/d in SMART and >32 salbutamol actuations/d in Standard) were assessed by multivariate analyses. Results FEV1 % predicted (rate ratio [RR] 1.14 [95% CI, 1.03-1.27] per 10% lower), more previous exacerbations (RR 1.15 [95% CI, 1.01-1.31]), Standard therapy (RR 1.62 [95% CI, 1.07-2.47]), and female sex (RR 2.18 [95% CI, 1.29-3.67]) were associated with future severe exacerbations. Asthma Control Questionnaire–5 (regression coefficient 0.20 [95% CI, 0.13-0.27] per 0.5 points higher) and age (regression coefficient 0.09 [95% CI, 0.01-0.17] per decade older) were associated with future poorly controlled asthma. Higher reliever use (RR 1.63 [95% CI, 1.36-1.95] per categorical score in Asthma Control Questionnaire question no. 6), Māori ethnicity (RR 2.20 [95% CI, 1.43-3.38]) and FEV1 % predicted (RR 1.16 [95% CI, 1.03-1.31] per 10% lower) were associated with future extreme β-agonist overuse. Conclusion Future severe asthma exacerbations, poor asthma control, and extreme β-agonist overuse are predicted by different baseline clinical and demographic characteristics and management approaches in at-risk asthma.