We analyzed the data of a randomized controlled trial to examine the effects of piano practice on cognitive flexibility in healthy older adults. Participants (N = 153, 69.5 ± 3.5 years of age, 57.5% females) were randomly assigned to a piano practice group (PP) or a control group engaged in active music listening (MC). Both groups underwent a year-long intervention with weekly 60-min lessons and daily homework. We assessed switch and mixing costs in terms of speed (mean reaction times) and variability (standard deviation of reaction times) with a number switch and a perceptual switch task. We employed scale analysis based on musical instrument digital interface to assess pianistic performance. Tests were conducted at baseline, after 6 months, postintervention (12 months), and at follow-up (18 months). Results revealed more pronounced improvements in pianistic performance in the PP group compared with the MC group over the course of the intervention. Both groups exhibited gains in several cognitive flexibility outcomes, which originated primarily in the latter half of the intervention. For mixing costs of the number switch test, the PP group showed greater improvements compared with the MC group. Changes in pianistic performance were not related to changes in cognitive flexibility. Additionally, the findings indicated a compensation account in both groups, which was more pronounced in the PP group for mixing costs. This study suggests that both piano practice and active music listening—with piano practice to a higher degree—enhance cognitive flexibility, particularly in sustained control mechanisms linked to mixing costs. Both interventions potentially require longer than 6 months to induce behavioral transfer effects and are especially beneficial for individuals with lower cognitive flexibility levels. Impact Statement : This study suggests that piano practice and active analytical musical listening activities can enhance cognitive flexibility, a cognitive function that is particularly vulnerable in older age. This beneficial effect appears to be particularly pronounced in people with low levels of cognitive flexibility. However, these functions exhibit limited short-term sensitivity to such interventions, indicating that a longer duration (about 12 months as in our study) is necessary for the behavioral effects to manifest.