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BACKGROUND The Trial of Nonpharmacologic Interventions in the Elderly (TONE) demonstrated the efficacy of weight loss and sodium reduction to reduce hypertension medication use in older adults. However, the longer-term effects of drug withdrawal (DW) on blood pressure (BP), adverse events, and orthostatic symptoms were not reported. METHODS TONE enrolled adults, ages 60-80 yrs, receiving treatment with a single antihypertensive and systolic BP (SBP)/diastolic BP (DBP) <145/<85 mmHg. Participants were randomized to weight loss, sodium reduction, both, or neither (usual care) and followed up to 36 months; ~3 months post-randomization, the antihypertensive was withdrawn and only restored if needed for uncontrolled hypertension. BP and orthostatic symptoms (light-headedness, feeling faint, imbalance), were assessed at randomization and throughout the study. Two physicians independently adjudicated adverse events, masked to intervention, classifying symptomatic (lightheadedness, dizziness, vertigo) or clinical events (fall, fracture, syncope). RESULTS Among the 975 participants (mean age 66 yrs, 48% women, 24% black), mean (±SD) BP was 128±9/71±7 mmHg. Independent of assignment, DW increased SBP by 4.59 mmHg (95% CI:3.89,5.28) compared to baseline. There were 113 adverse events (84 symptomatic, 29 clinical), primarily during DW. Compared to usual care, combined weight loss and sodium reduction mitigated the effects of DW on BP (β=-4.33 mmHg;95%CI:-6.48,-2.17) and reduced orthostatic symptoms long-term (OR=0.62;95%CI:0.41,0.92), without affecting adverse events (HR=1.81;95%CI:0.90,3.65). In contrast, sodium reduction alone increased risk of adverse events (HR=1.75;95%CI:1.04,2.95), mainly during DW. CONCLUSION In older adults, antihypertensive DW may increase risk of symptomatic adverse events, highlighting the need for caution in withdrawing their antihypertensive medications.