The clinical outcomes of patients with non-ST-segment elevation myocardial infarction (NSTEMI) were comparable or even worse than those with ST-segment elevation myocardial infarction (STEMI). Although successful percutaneous coronary intervention (PCI) to the culprit lesions of NSTEMI would improve the clinical outcomes, some PCI require long fluoroscopy time, reflecting the difficulty of PCI. This study aims to find clinical factors associated with long fluoroscopy time in PCI to the culprit lesion of NSTEMI. We included 374 patients and divided those into the conventional fluoroscopy time (n = 302) and long fluoroscopy time (n = 72) groups according to the quintiles of fluoroscopy time. Clinical and angiographic parameters were compared between the two groups. Calcification and tortuosity were significantly more severe in the long fluoroscopy time group than in the conventional fluoroscopy time group. The prevalence of previous coronary artery bypass grafting (CABG) and bifurcation lesions was significantly greater in the long fluoroscopy time group than in the conventional fluoroscopy time group. In the multivariate stepwise logistic regression analysis, previous CABG (odds ratio [OR], 3.368; 95% confidence interval [CI], 1.407-8.064; P = 0.006), bifurcation lesion (OR, 2.407; 95% CI, 1.285-4.506; P = 0.006), excessive tortuosity (versus mild to moderate tortuosity; OR, 4.095; 95% CI, 1.159-14.476; P = 0.029), and moderate to severe calcification (versus none to mild; OR, 5.792; 95% CI, 3.254-10.310; P < 0.001) were significantly associated with long fluoroscopy time. In conclusion, previous CABG, bifurcation, excessive tortuosity, and moderate to severe calcification were associated with long fluoroscopy time. Our study provided a reference for PCI operators to identify the difficulties in PCI to the culprit lesion of NSTEMI.