Importance: Postoperative delirium (POD) is a common condition for older adults, contributing to their functional decline.; Objective: To investigate the effectiveness of the Tailored, Family-Involved Hospital Elder Life Program (t-HELP) for preventing POD and functional decline in older patients after a noncardiac surgical procedure.; Design, Setting, and Participants: A 2-arm, parallel-group, single-blind, cluster randomized clinical trial was conducted from August 24, 2015, to February 28, 2016, on 6 surgical floors (gastric, colorectal, pancreatic, biliary, thoracic, and thyroid) of West China Hospital in Chengdu, China. Eligible participants (n = 281) admitted to each of the 6 surgical floors were randomized into a nursing unit providing t-HELP (intervention group) or a nursing unit providing usual care (control group). All randomized patients were included in the intention-to-treat analyses for the primary outcome of POD incidence. Statistical analysis was performed from April 3, 2016, to December 30, 2017.; Interventions: In addition to receiving usual care, all participants in the intervention group received the t-HELP protocols, which addressed each patient's risk factor profile. Besides nursing professionals, family members and paid caregivers were involved in the delivery of many of the program interventions.; Main Outcomes and Measures: The primary outcome was the incidence of POD, evaluated with the Confusion Assessment Method. Secondary outcomes included the pattern of functional and cognitive changes (activities of daily living [ADLs], instrumental activities of daily living [IADLs], Short Portable Mental Status Questionnaire [SPMSQ]) from hospital admission to 30 days after discharge, and the length of hospital stay (LOS).; Results: Of the 475 patients screened for eligibility, 281 (171 [60.9%] male, mean [SD] age 74.7 [5.2] years) were enrolled and randomized to receive t-HELP (n = 152) or usual care (n = 129). Postoperative delirium occurred in 4 participants (2.6%) in the intervention group and in 25 (19.4%) in the control group, with a relative risk of 0.14 (95% CI, 0.05-0.38). The number needed to treat to prevent 1 case of POD was 5.9 (95% CI, 4.2-11.1). Participants in the intervention group compared with the control group showed less decline in physical function (median [interquartile range] for ADLs: -5 [-10 to 0] vs -20 [-30 to -10]; P < .001; for IADLs: -2 [-2 to 0] vs -4 [-4 to -2]; P < .001) and cognitive function (for the SPMSQ level: 1 [0.8%] vs 8 [7.0%]; P = .009) at discharge, as well as shorter mean (SD) LOS (12.15 [3.78] days vs 16.41 [4.69] days; P < .001).; Conclusions and Relevance: The findings suggest that t-HELP, with family involvement at its core, is effective in reducing POD for older patients, maintaining or improving their physical and cognitive functions, and shortening the LOS. The results of this t-HELP trial may improve generalizability and increase the implementation of this program.; Trial Registration: Chinese Clinical Trial Registry Identifier: ChiCTR-POR-15006944.