Multinutrient protein-enriched supplements are promoted to augment the effects of exercise on muscle mass and strength, but their effectiveness in middle-aged women, or whether there are any additional benefits to physical function, remains uncertain. We aimed to evaluate whether a multinutrient-fortified milk drink (MFMD) could enhance the effects of exercise on functional muscle power (stair climbing) in middle-aged women. Secondary aims were to evaluate the intervention effects on physical function, muscle strength, lean mass (LM), fat mass (FM), bone mineral content (BMC), muscle cross-sectional area (CSA), muscle density, balance, flexibility, aerobic fitness, inflammation, oxidative stress, bone and cartilage turnover, blood pressure, and blood lipids. In this 4-mo, double-blind, placebo-controlled, randomized trial, 244 women (45-65 y) participated in a multimodal resistance-type exercise program 3 d/wk, with random allocation to a twice-daily MFMD containing added protein, vitamin D, calcium, milk fat globule membrane (phospholipids and other bioactives), and other micronutrients (Ex+MFMD, n=123) or an energy-matched placebo (Ex+placebo, n=121). A total of 216 women (89%) completed the study. After 4 mo, both groups experienced similar 3.6%-4.3% improvements in the primary outcomes of fast-pace 5- and 10-step stair ascent power. In contrast, Ex+MFMD experienced greater improvements in 5-step regular-pace stair descent time [net difference (95% CI): -0.09 s (-0.18, 0.00 s), P=0.045], countermovement jump height [0.5 cm (0.04, 1.0 cm), P=0.038], total body LM [0.3 kg (0.04, 0.60 kg), P=0.020], FM [-0.6 kg (-1.0, -0.2 kg), P=0.004], BMC [0.4% (0.1%, 0.6%), P=0.020], muscle CSA [thigh: 1.8% (0.6%, 2.9%), P=0.003; lower leg: 0.9% (0.3%, 1.6%), P=0.005], balance eyes closed [3.3 s (1.1, 5.4 s), P=0.005], 2-min step performance [8 steps (3, 12 steps), P=0.003], and sit-and-reach flexibility [1.4 cm (0.6, 2.2 cm), P=0.026]. MFMD did not enhance the effects of exercise on any measures of muscle strength, gait speed, dynamic balance, reaction time, or blood lipids, and there was no effect of either intervention on blood pressure, markers of inflammation, or cartilage turnover. Ex+placebo had a greater improvement in the oxidative stress marker protein carbonyls (P<0.01). In middle-aged women, daily consumption of an MFMD did not enhance the effects of a multimodal exercise program on the primary outcome of stair climbing ascent power, but did elicit greater improvements in multiple secondary outcomes including various other measures of functional performance, LM, muscle size, FM, balance, aerobic capacity, flexibility, and bone metabolism.This trial was registered at www.anzctr.org.au as ACTRN12617000383369.