Objectives This study aimed to investigate the association of serum alkaline phosphatase (ALP) with calcification patterns and plaque morphology detected by intravascular ultrasound (IVUS) in acute coronary syndrome (ACS) patients. Background ALP has been shown to predict vascular calcification and long-term cardiovascular events. However, the relationship between ALP and vascular calcification patterns or plaque morphology remains unclear. Methods In total, 328 ACS patients who underwent IVUS examinations were screened from January 2017 to December 2018; among them, 234 eligible participants were grouped according to the tertiles of ALP levels (<68, 68-80, and >80 IU/L). Demographic data and IVUS parameters were documented and analyzed. Results After adjusting for potential confounders, independent associations were observed between ALP and the presence of coronary calcification, spotty calcification, minimum lumen area (MLA) <= 4.0 mm(2), and plaque burden (PB) > 70%. Compared with the lowest ALP tertile group, the highest ALP group had higher risks of calcification (odds ratio [OR], 2.85; 95% confidence interval [95%CI], 1.38-5.90; p = .005), spotty calcification (OR, 1.86; 95%CI, 1.09-3.84; p = .012), MLA <= 4.0 mm(2) (OR, 3.32; 95%CI, 1.51-7.28; p = .003), and PB > 70% (OR, 4.59; 95%CI, 1.83-11.50; p = .001). Similar results were found when ALP was analyzed as a continuous variable or a category variate according to the cut-off value determined by the receiver operating characteristic curve analysis. Furthermore, the model including clinical factors and ALP significantly improved the predictive power for coronary calcification, spotty calcification, MLA <= 4.0 mm(2), and PB > 70%. Conclusion Our findings suggest that ALP may be a potential predictive biomarker for calcification and plaque vulnerability.