Importance Older adults undergoing major noncardiac surgery experience substantial postoperative morbidity and health care use. The comparative effectiveness of total intravenous anesthesia (TIVA) vs volatile-based inhalational anesthesia on recovery and safety remains uncertain. Objectives To determine whether TIVA improves days alive and at home at 30 days compared with inhalational anesthesia and to evaluate differences in patient-centered outcomes and recovery. Design, Setting, and Participants Pragmatic, multicenter, open-label randomized clinical trial conducted in 49 UK National Health Service hospitals from January 2022 to April 2024 (final follow-up, October 2024) among patients aged 50 years or older scheduled for elective major noncardiac surgery. Interventions Participants were randomized 1:1 to receive maintenance of general anesthesia with either TIVA (propofol infusion) (n = 1254) or volatile-based inhalational agents (n = 1254). All other perioperative care was at clinician discretion. Main Outcomes and Measures The primary outcome was days alive and at home at 30 days. Secondary outcomes included days alive and at home at 90 days; mortality at 30 days, 90 days, and 6 months; Quality of Recovery–15 score at day 3; patient satisfaction (Bauer Patient Satisfaction Questionnaire) at day 1; delirium (4 As Test [4AT]) at day 3; unintentional awareness under anesthesia; and major postoperative complications within 30 days. Results Among the 2508 randomized participants, the mean age was 67 (SD, 8.9) years, and 55% were male. Characteristics were balanced across randomized groups. Days alive and at home at 30 days were similar between groups (mean, 22.5 [SD, 6.8] days vs 22.4 [SD, 6.6] days for TIVA vs inhalational anesthesia, respectively; incidence rate ratio, 1.00; 95% CI, 0.99-1.02; adjusted P = .68). There were no differences in days alive and at home at 90 days; mortality at 30 days, 90 days, or 6 months; or Quality of Recovery–15 score at day 3. Lower rates of thirst, hoarseness, and nausea and vomiting were reported in the TIVA group. Levels of delirium were similar between groups, with the majority (87.6%) having no delirium at day 3. Major complications occurred in 12.4% of patients overall, with no significant between-group differences. Two cases of certain or probable unintentional awareness under anesthesia were reported, both in the TIVA group. Conclusions and Relevance Among older adults undergoing major noncardiac surgery, TIVA did not improve days alive and at home at 30 days compared with inhalational anesthesia. Trial Registration ISRCTN.org Identifier: ISRCTN62903453