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<b>Objective:</b> To investigate the association between baseline cumulative atherogenic index of plasma and the risk of new-onset cardiovascular disease in middle-aged and young populations. <b>Methods:</b> A total of 35 212 populations under 60-years old with complete physical examination in 2006 and 2010 from the Kailuan Study were retrospectively enrolled. Complete atherogenic index of plasma data were extracted and populations were grouped by cumulative atherogenic index of plasma quartile: Q1 group (<-0.80, <i>n</i>=8 803), Q2 group (-0.80-<-0.19, <i>n</i>=8 803), Q3 group (-0.19-<0.49, <i>n</i>=8 803), Q4 group (≥0.49, <i>n</i>=8 803). The study subjects were followed up, with the endpoint defined as the occurrence of new-onset cardiovascular disease, defined as myocardial infarction and stroke. The follow-up period began after the physical examination in 2010 and ended at the date of the endpoint event or December 31, 2022, whichever came first. Cox proportional hazard regression model was used to analyze the impact of cumulative atherogenic index of plasma on the risk of new-onset cardiovascular disease and its subtypes, with trend tests conducted. Stratification was performed based on hypertension status, diabetes status, and low-density lipoprotein cholesterol (LDL-C) levels (<3.4 mmol/L or ≥3.4 mmol/L) to examine multiplicative interactions with the cumulative atherogenic index of plasma, and Cox proportional hazards regression analysis was subsequently conducted. <b>Results:</b> Among 35 212 participants, 26 636 (75.6%) were male, with an age of (45.4±8.3) years. Cardiovascular disease occurred in 2 075 cases (5.9%), of which 390 (1.1%) had myocardial infarction and 1 725 (4.9%) had stroke. During a follow-up of (11.5±2.0) years, the incidence densities of new-onset cardiovascular disease from Q1 to Q4 groups were 3.08, 4.70, 5.55 and 7.23 per 1 000 person-years, respectively. Cox proportional hazard regression model showed that, compared with the Q1 group, after adjusting for confounding factors, the <i>HRs</i>(95%<i>CIs</i>) of cardiovascular disease in Q2, Q3 and Q4 groups were 1.27 (1.10-1.48), 1.33 (1.14-1.56), 1.43 (1.19-1.72), respectively, the differences were statistically significant (all <i>P</i><0.05). The risk of cardiovascular disease showed an increasing trend across the Q1 to Q4 groups (<i>P</i><sub>trend</sub><0.001). In the endpoint-specific analyses for myocardial infarction and stroke, stroke demonstrated a similar trend (<i>P</i><sub>trend</sub>=0.002), while no statistically significant difference was observed for myocardial infarction (<i>P</i><sub>trend</sub>=0.465). Subgroup analysis showed that there were potential multiplicative interactions between different levels of LDL-C, the presence or absence of hypertension or diabetes, and the cumulative atherogenic index of plasma (all <i>P</i> for interaction<0.05). In a low-risk population with LDL-C<3.4 mmol/L, non-hypertensive, or non-diabetic, the cardiovascular disease risk in the Q4 group increased by 48%, 59%, and 49% compared to the Q1 group (all <i>P</i><0.05), respectively. <b>Conclusions:</b> In the middle-aged and young populations, a high level of cumulative atherogenic index of plasma is associated with an increased risk of cardiovascular disease. This elevated risk is independent of the effects of traditional risk factors and remains significant even among low-risk populations.