The most effective method of image guidance for venovenous extracorporeal membrane oxygenation is not known. The authors' objectives were to define the frequency of successful initial cannulation using echocardiographic guidance in the intensive care unit, as well as to determine the frequency of subsequent adjustments. Additional aims were to illustrate cannula malposition problems and to describe features associated with difficult cannulation. Retrospective consecutive case series analysis. Single tertiary care university hospital. Forty-five patients treated with venovenous extracorporeal membrane oxygenation. None. The most common causes of respiratory failure were pneumonia, aspiration, and inhalational burn injury. Sixty-two percent survived to discharge. Initial cannulation was successful in 39 cases (87%). Adverse events included 5 cases of cannula malposition and 1 case of hemorrhagic shock. During the course of extracorporeal membrane oxygenation, 17 patients (38%) required echo-guided cannula position adjustments. There were no fatal complications. Factors associated with difficult cannulation included extremes of size, a prominent Eustachian valve, and an anterior guidewire bending in the right atrium. Younger age was associated positively with survival. There was no significant association between adverse events during cannulation and survival. Dual-lumen venovenous extracorporeal membrane oxygenation cannulation in the intensive care unit under echo guidance has a high initial success rate, but many patients require subsequent repositioning. Echocardiography can define cannula position in sufficient detail to identify malposition precisely and to guide repositioning.