Purpose: This study analyzed longitudinal data to examine whether occupational sitting time is associated with increases in body mass index (BMI) and five-year cardiovascular disease (CVD) risk. Methods: We included 2,000 employed men and women (aged 31–60) from the German Study on Mental Health at Work (S-MGA) for a BMI analysis and 1,635 participants free of CVD at baseline (2011/2012) for a CVD analysis. Occupational sitting time was categorized into five groups (< 5, 5 to < 15, 15 to < 25, 25 to < 35, and ≥ 35 h per week). BMI change was measured from baseline (2011/2012) to follow-up (2017). Incident CVD included hypertension, heart disease, myocardial infarction, and stroke (all self-reported). Multiple linear regression examined the association between sitting time and BMI change, while modified Poisson regression analyzed CVD incidence, adjusting for age, sex, occupation, shift work, leisure activity, and smoking by sex. Covariates were self-reported. Results: Over five years, the average BMI change was 0.49 (SD 1.9). We found no association between baseline occupational sitting time and BMI changes, with consistent results in sensitivity analyses. During this period, 245 participants developed cardiovascular disease. There was no increased risk of CVD among those with more sitting time compared to less. No differences in risk were found between women and men. Conclusion: There was no association between occupational sitting time and five-year changes in BMI or incident CVD.