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To determine the association of resistance exercise, independent of and combined with aerobic exercise, with the risk of development of metabolic syndrome (MetS).The study cohort included adults (mean ± SD age, 46±9.5 years) who received comprehensive medical examinations at the Cooper Clinic in Dallas, Texas, between January 1, 1987, and December, 31, 2006. Exercise was assessed by self-reported frequency and minutes per week of resistance and aerobic exercise and meeting the US Physical Activity Guidelines (resistance exercise ≥2 d/wk; aerobic exercise ≥500 metabolic equivalent min/wk) at baseline. The incidence of MetS was based on the National Cholesterol Education Program Adult Treatment Panel III criteria. We used Cox regression to generate hazard ratios (HRs) and 95% CIs.Among 7418 participants, 1147 (15%) had development of MetS during a median follow-up of 4 years (maximum, 19 years; minimum, 0.1 year). Meeting the resistance exercise guidelines was associated with a 17% lower risk of MetS (HR, 0.83; 95% CI, 0.73-0.96; P=.009) after adjusting for potential confounders and aerobic exercise. Further, less than 1 hour of weekly resistance exercise was associated with 29% lower risk of development of MetS (HR, 0.71; 95% CI, 0.56-0.89; P=.003) compared with no resistance exercise. However, larger amounts of resistance exercise did not provide further benefits. Individuals meeting both recommended resistance and aerobic exercise guidelines had a 25% lower risk of development of MetS (HR, 0.75; 95% CI, 0.63-0.89; P<.001) compared with meeting neither guideline.Participating in resistance exercise, even less than 1 hour per week, was associated with a lower risk of development of MetS, independent of aerobic exercise. Health professionals should recommend that patients perform resistance exercise along with aerobic exercise to reduce MetS.