Introduction: Ultrasound-guided intravenous (UGIV) insertion performed by nurses has been shown to be more effective than the blind approach for patients with difficult intravenous (IV) access in the emergency department (ED). While both the single-operator (SO) (where a single operator holds the IV and probe) and dual-operator (DO) (where a second operator holds the probe) techniques have been described, the DO is more resource-intensive, requiring a second operator to be present. The objective of this study is to compare the first-attempt cannulation success rates between a SO and DO technique in ED patients with predicted difficult access. Methods: We conducted a randomized controlled non-inferiority trial using a convenience sample of adult ED patients. Participating ED nurses received a one-hour UGIV training session including didactic and practical training on simulated arms. Patients were enrolled if they met any of three criteria for difficult access: (1) history of difficult access, (2) no visible or palpable veins, or (3) two failed blind attempts. Patients requiring active resuscitation, lack of suitable veins on US, or those unable to consent or comply with the procedure were excluded. Eligible patients were randomized to the SO or DO technique and a maximum of two UGIV attempts were allowed. The primary outcome was first-attempt success rate. Additional outcomes included overall success rate, number of attempts, time to successful cannulation, patient pain scores, operator ease of use scores, and complications 30 minutes after insertion. The chi-square test was used to compare success rates between groups and t-tests used for all other secondary outcomes. Results: 42 eligible patients have been approached for our study. 14 were excluded due to lack of visible veins on US or due to ongoing resuscitation. A total of 33 UGIV attempts were performed on 28 patients (17 in SO group, 16 in DO group). There was no statistically significant difference in first attempt success rates between the SO group of 76.5% (95% CI [50.1% to 93.2%]) and the DO group of 68.8% (95% CI [41.3% to 89%]) (p=0.62). There were also no statistically significant differences between the SO and DO groups in time to cannulation (140 vs 165 seconds, p=0.36), patient preference on a 10-point scale (7.0 vs 7.9, p=0.49), patient pain score (6.3 vs 6.6, p=0.87) or nursing ease of use (5.3 vs 6.5 p=0.23) respectively. There were no complications noted in either arm of the study. Conclusion: To date, the SO technique appears to be non-inferior to the DO technique for successful UGIV cannulation. Our results support the use of the SO technique, reducing the need for additional nursing resources when performing this procedure.