High adherence to the Mediterranean diet (MD) has been associated with lower incidence of cardiovascular disease, increased HDL-cholesterol levels, and decreased triglycerides (TG), and total and LDL cholesterol levels. We aimed to assess the association of MD adherence at baseline with the lipid profile both cross-sectionally and prospectively in a sample of apparently healthy community-dwelling subjects. We conducted three cross-sectional studies using data from follow-ups 1 (FU1, 2009-2012), 2 (FU2, 2014-2017), and 3 (FU3, 2018-2021) of CoLaus|PsyCoLaus, a population-based sample from Lausanne, Switzerland. Dietary intake was assessed with a food frequency questionnaire. Two MD scores (Trichopoulou and Vormund) were computed, ranging from 0 (low) to 9 (high). In total, LDL and HDL cholesterol and TG were assessed. Incident dyslipidemia was defined as hypolipidemic treatment at FU2 or FU3. Overall, 4249 participants from FU1 (53.7% women, 57.6 ± 10.5 years, Trichopoulou 4.0 ± 1.5, Vormund 4.7 ± 1.9) were included. Neither MD score correlated significantly with the lipid markers and similar results were obtained according to the hypolipidemic status. Among the 3092 untreated FU1 participants with FU2 and FU3 data, 349 (11.3%) developed dyslipidemia by FU2 or FU3. No difference in MD scores was found between participants who developed dyslipidemia and those who did not (4.1 ± 1.5 vs. 4.0 ± 1.5 and 4.8 ± 1.8 vs. 4.8 ± 1.9 for Trichopoulou and Vormund, respectively, p > 0.05). Finally, no associations were found between MD score and lipid changes at 5 or 10 years. Contrary to other studies, adherence to MD at baseline did not show any significant effects on lipid composition/incident dyslipidemia in Colaus|PsyCoLaus participants.