<p>The long-term impact of common cardiovascular medications on sarcopenia in older people is unclear. The objective was to investigate whether long-term intake of statins and renin–angiotensin system inhibitors (RASi), i.e., angiotensin-converting enzyme inhibitors (ACEi) or angiotensin receptor blockers (ARB), is associated with muscle mass, strength, and physical performance in community-dwelling older adults. This exploratory observational cohort study included 1083 participants of the Berlin Aging Study II (52% women, 68.3 ± 3.5 years at baseline) with an extended follow-up of 7.4 ± 1.5 years. Statins or RASi users at baseline and follow-up were compared with nonusers. Appendicular lean mass (ALM) was measured via dual-energy X-ray absorptiometry and related to body mass index (ALM/BMI) and height² (SMI). Hand grip strength, arm muscle quality, the Timed “up and go,” and Tinetti mobility test were additionally assessed. Adjusted linear regressions of drug use on muscle-related parameters were conducted. Statin use was not associated with any of the muscle-related outcomes. RASi use was associated with modestly lower ALM/BMI (<i>β</i> = −0.036, <i>p</i> = 0.004). Sex-stratified analyses showed that RASi use was significantly associated with lower ALM/BMI in women (<i>β</i> = −0.033, <i>p</i> = 0.029) but not in men (<i>β</i> = −0.037, <i>p</i> = 0.072), without a significant sex interaction. Long-term statin use was not associated with sarcopenia-related parameters, which is clinically reassuring. RASi use showed a modest association with lower ALM/BMI, but causality cannot be inferred because of the exploratory design. These findings warrant replication in independent cohorts and suggest that the clinical relevance of this association should be further evaluated.</p> Graphical Abstract <p></p>