Introduction: The prevalence of obesity is high and increasing worldwide. Obesity is generally associated with an increased risk of chronic disease and mortality. The objective of the study was to test the effect of a lifestyle intervention on body weight and other chronic disease risk markers. Methods: A non-randomized controlled trial was conducted, including mostly middle-aged and elderly participants recruited from the general population in rural northwest Germany (intervention: n = 114; control: n = 87). The intervention consisted of a 1-year lifestyle programme, focussing on four key areas: a largely plant-based diet (strongest emphasis), physical activity, stress management, and community support. Parameters were assessed at baseline, 10 weeks, 6 months, and 1 year. The control group received no intervention. Results: Compared to the control, in the intervention group, significantly lower 1-year trajectories were observed for body weight, body mass index (BMI), waist circumference (WC), total cholesterol, calculated LDL cholesterol, non-HDL cholesterol, remnant cholesterol (REM-C), glucose, HbA1c, and resting heart rate (RHR). However, between-group differences at 1 year were small for glucose, HbA1c, and cholesterol (apart from REM-C). No significant between-group differences were found for 1-year trajectories of measured LDL cholesterol, HDL cholesterol, triglycerides, insulin, blood pressure, and pulse pressure. Conclusion: The intervention successfully reduced body weight, BMI, WC, REM-C, and RHR. However, at 1 year, effectiveness of the intervention regarding other risk markers was either very modest or could not be shown.