Background: Several lines of evidence have supported small dense low-density lipoproteins (sd-LDL) as a marker of cardiovascular disease. The present study assessed the relationship between lipid profile and sd-LDL levels with demographic, clinical, angiographic, and therapeutic variables in acute coronary syndrome (ACS) patients. Methods: This was a single-centre, prospective, cross-sectional study conducted from September 2014 to September 2015. Patients with a diagnosis of ACS were included in this study. High-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) were determined by direct homogenous assay and sd-LDL levels were calculated using an earlier described equation by Srisawadi et al. Results: A total of 200 patients with a diagnosis of ACS were studied. Males constituted 78% of the population cohort and almost 45% of participants were aged <45 years. Patients aged ≤45 years displayed higher mean sd-LDL levels of 30.40 ± 14.18 mg/dL versus patients aged >45 years with mean sd-LDL levels of 28.01 ± 11.58 mg/dL, but the difference was not statistically significant (p = 0.19). Females also displayed higher mean sd-LDL levels, but the difference also failed to achieve statistical significance (30.95 ± 13.44 mg/dL and 28.54 ± 12.64, respectively; p = 0.185). Diabetics had higher mean sd-LDL levels (33.64 ± 13.01 mg/dL and 28.07 ± 12.60 mg/dL; p = 0.273) whilst smokers had lower mean levels (27.21 ± 12.12 mg/dL and 30.51 ± 13.21 mg/dL, respectively; p = 0.071). However, the ratio of sd-LDL/lb-LDL (large buoyant LDL) was significantly higher in diabetics (0.48 vs. 0.39; p = 0.023). In the angiography cohort (n = 88), single-vessel disease was the most predominant overall while among patients aged >45 years, triple-vessel disease was significantly higher (p = 0.005). Similarly, the sd-LDL levels were 33.12 ± 11.13 mg/dL, 27.68 ± 9.80 mg/dL, and 31.65 ± 15.26 mg/dL among patients with single, double, and triple-vessel disease and did not differ significantly (p = 0.262). Prior statin users had significantly lower mean sd-LDL levels of 24.79 ± 12.23 mg/dL compared to statin-naïve patients with a mean sd-LDL of 30.01 ± 12.79 mg/dL (p = 0.027). Non-HDL levels were also significantly lower in prior statin users (112.83 mg/dL vs. 128.9 mg/dL; p = 0.017). Conclusion: In this cohort of ACS patients, age, sex, diabetes, smoking, and the angiographic severity of coronary artery disease had no significant impact on sd-LDL levels, while prior statin usage led to significantly lower sd-LDL levels. Diabetic patients, however, did have significantly higher sd-LDL/lb-LDL ratios.