Introduction Smoking is the most preventable cause of cardiovascular disease (CVD).Dyslipidemia is also an important risk factor for CVD. Yet, research has provided contradicting findings regarding the association between smoking and blood lipids. This study aims to assess the relationship between smoking and dyslipidemia, as well as compliance with the previously established treatment target. Materials and methods This was a cross-sectional study. Apparently, healthy users aged 40 or over, were from four primary health care units (PHCU) in Portugal. The inclusion criteria were: age between 40 and 69 and active enrollment in one of the four PHCU. The exclusion criteria were: background of atherosclerotic disease, heart failure, chronic kidney disease, diabetes mellitus, and a history of acute myocardial infarction; no record of lipid profile or triglyceride value of more than 400 mg/dL.Cardiovascular risk levels were determined using the Systematic Coronary Risk Evaluation (SCORE) 2 risk. The low-density lipoprotein cholesterol (LDL-c) target was considered the recommendation by the European Society of Cardiology/European Atherosclerosis Society (ESC/EAS) 2019. Results From an initial population of 16,939 patients, 12,076 apparently healthy patients were included.The difference between cholesterol values is statistically significant, with total cholesterol, LDL-c, and triglyceride values tending to be higher in the smoking group and the high-density lipoprotein cholesterol (HDL-c) value tending to be higher in the non-smoking group. Regarding the LDL target, there is also a statistically significant difference between smokers and non-smokers. Discussion Smoking and dyslipidemia are two isolated cardiovascular risk factors. Their association has been questioned. This study demonstrated that there is an association between smoking and the lipid profile, but also with the LDL target. However, there are some biases that must be considered, and which do not allow for generalization. Conclusions This study concludes that smoking negatively influences the lipid profile, with lipids being found less frequently on target. However, more studies are needed in this area, particularly studying other relevant factors such as body mass index.