Objective: To determine if weight gain is accompanied by development of insulin resistance (IR) during 4 years in college. Participants: Two cohorts of college students were enrolled in fall semesters 2009 and 2010 and tracked for 4 years. Methods: Following a 12-hour fast, subjects reported for measurement of body mass index (BMI), perceived stress (PSS), aerobic fitness, and blood glucose, insulin, and lipids. Results: In the first year, 33% of subjects were overweight or obese, and 20% were hyperinsulinemic. Year 4 had 29 remaining subjects with disproportionate attrition of overweight and obese individuals. Just over half the subjects gained weight (WI), whereas nearly 30% lost considerable amounts (WD). WD showed significant decline in fasting insulin, low-density lipoprotein (LDL) cholesterol, and PSS from year 1. WI was primarily highly fit men who did not demonstrate increased IR. Conclusion: WI was not associated with IR over 4 years of college.