Objective To explore the influence of enoxaparin on clinical events in complicated coronary lesions after percutaneous coronary intervention (PCI). Methods Totally 288 patients with complicated coronary lesions (type B2 and type C), who had no notable complications following PCI, were recruited in the present study. The patients were randomly assigned to receive either enoxaparin or not. Patients were assessed for major adverse cardiac events (MACEs) during hospitalization and at 1 and 12 months after PCI. Results There were no significant differences in the frequency of MACEs between the two groups during hospitalization (2.1% vs 1.4%, P>0.05), at 1 month (2.8% vs 2.8%, P>0.05) or 12 months post-PCI (5.5% vs 6.3%, P=0.780). The cumulative incidence rates of MACEs were not significantly different between the two groups (HR=0.875, 95%CI 0.337-2.273; P=0.79). The two groups had comparable rates of major bleeding (4.8% vs 2.8%, P=0.369), but that of the minor bleeding was significantly higher in the anticoagulation group (26.2% vs 16.1%, P=0.036). The average hospital stay in the anticoagulation group were significantly longer than that in the non-anticoagulation group ([6.04±1.64] d vs [5.43±1.54] d, P=0.001). Conclusion MACEs after PCI is not increased in patients with complicated coronary lesions receiving no anticoagulation compared with those receiving, with less minor bleeding and shorter hospital stay, suggesting that for the patients with complicated coronary lesions, routine anticoagulation therapy is not necessary after PCI without procedure complications.