Estimation of the fractional flow reserve (FFR) is considered to be an established method by which to assess stable coronary artery stenosis. Induction of maximal coronary hyperemia is important during the FFR procedure. Papaverine has been reported to increase the risk of ventricular arrhythmia (VA). The purpose of the present study was to discover predictors of papaverine-induced VAs developing during FFR measurement. A total of 213 clinically stable patients were included in the study. FFRs were determined after intracoronary papaverine administration (12 mg into the left and 8 mg into the right coronary arteries). We compared patients in whom VA did and did not develop in terms of clinical and electrocardiogram characteristics. FFR measurements were performed on 244 lesions (133 in the left anterior descending arteries, 43 in the left circumflex arteries, and 68 in the right coronary arteries). We found that the QTc interval was prolonged in all patients after papaverine administration (average post-administration QTc interval = 569 ± 89 ms; average ΔQTc interval = 144 ± 80 ms). VA developed in three patients with significantly prolonged QT intervals (average post-administration QTc interval = 639 ± 19 ms, average ΔQTc interval = 220 ± 64 ms, p < 0.02) and transitioned from torsade de pointes to ventricular fibrillation. Bradycardia (< 50 beats/min), hypokalemia (serum K < 3.5 mEp/L), and low left ventricular function (ejection fraction (EF) < 50%) were associated with VA (bradycardia, p < 0.01; hypokalemia, p < 0.01; low left ventricular function, p < 0.01). Three-vessel disease was significantly predictive of VA (p < 0.003). In the three-vessel group, the complications of low left ventricular function, hypokalemia, and bradycardia were significantly associated with VA (p < 0.045). Three-vessel disease is a predictor of the development of VA during FFR measurement performed with the aid of papaverine, especially if accompanied by one or more of the following: low left ventricular function, hypokalemia, or bradycardia.