Although rotational ablation has been successful in the treatment of complex coronary lesions, periprocedural complications of microvascular-mediated ischemia (slow flow or no reflow) and coronary vasospasm may occur. In an attempt to reduce such complications, a drug cocktail consisting of a combination of verapamil 10 micrograms/ml, nitroglycerin 4 micrograms/ml, and heparin 20 U/ml was infused in 21 consecutive patients with AHA/ACC Type B2 and C lesion morphology. A total of 27 lesions were treated, with a procedural success rate of 95%. One patient required emergency bypass surgery. Coronary vasospasm occurred in 7% (2/27 lesions). Only one lesion (3.7%) was associated with a transient reduction in TIMI flow that resolved within 5 min, and none had classical no-reflow. No patient developed intraluminal thrombus, and none had hypotension requiring inotropic support. All patients had prophylactic temporary pacemakers inserted. All RCA and circumflex lesions and 50% of LAD stenoses required transient pacing. A "cocktail" infusion of verapamil, nitroglycerin, and heparin mixed in pressurized saline delivered through the 4-French Teflon sheath of the Rotablator system during rotational ablation is associated with high success and low complication rates. Transient AV block is frequent, especially when treating RCA and circumflex arteries; therefore, prophylactic pacing is indicated.