Participating in muscle-strengthening activities (MSA) has been shown to reduce the risks associated with many individual chronic diseases; however, the impact of MSA on multimorbidity remains unexplored. Therefore, the purpose of this study was to determine the association between MSA and multimorbidity.Data from the 2003–2006 NHANES were used including 4587 adults (≥20years old). Participation in MSA was defined as self-reported involvement within the last 30days. Multimorbidity was deemed as having ≥2 of the 14 chronic diseases.After adjustments (including accelerometry-assessed physical activity), individuals participating in MSA had a 26% reduced odds of having multimorbidity (OR=0.74; 95% CI: 0.62–0.88; p=0.001) and each 2day/week increase in MSA was associated with an 8% reduced odds of being multimorbid (OR=0.92; 95% CI: 0.84–1.00; p=0.05).Independent of accelerometry-assessed physical activity, the participation in MSA may reduce the odds of being multimorbid, with evidence of a dose–response relationship.