Background Lifestyle modification is a key component of cardiovascular disease prevention before and concurrently with pharmacologic interventions. We evaluated whether lifestyle factors change in relation to the initiation of antihypertensive or lipid‐lowering medication (statins). Methods and Results The study population comprised 41 225 participants of the FPS (Finnish Public Sector) study aged ≥40 years who were free of cardiovascular disease at baseline and responded to ≥2 consecutive surveys administered in 4‐year intervals in 2000–2013. Medication use was ascertained through pharmacy‐claims data. Using a series of pre–post data sets, we compared changes in body mass index, physical activity, alcohol consumption, and smoking between 8837 initiators and 46 021 noninitiators of antihypertensive medications or statins. In participants who initiated medication use, body mass index increased more (difference in change 0.19; 95% CI , 0.16–0.22) and physical activity declined (−0.09 metabolic equivalent of task hour/day; 95% CI , −0.16 to −0.02) compared with noninitiators. The likelihood of becoming obese (odds ratio: 1.82; 95% CI , 1.63–2.03) and physically inactive (odds ratio: 1.08; 95% CI , 1.01–1.17) was higher in initiators. However, medication initiation was associated with greater decline in average alcohol consumption (−1.85 g/week; 95% CI , −3.67 to −0.14) and higher odds of quitting smoking (odds ratio for current smoking in the second survey: 0.74; 95% CI , 0.64–0.85). Conclusions These findings suggest that initiation of antihypertensive and statin medication is associated with lifestyle changes, some favorable and others unfavorable. Weight management and physical activity should be encouraged in individuals prescribed these medications.