BackgroundThe placement of a peripheral venous cannulation is a procedure that all healthcare providers must be able to perform. AimThis study compared two simulation techniques of a peripheral venous cannulation (VC): low fidelity simulation (LFS) versus standardized patient (SP) in terms of efficiency. MethodsThis crossover randomized trial compared LFS to SP in VC placement for 2nd year nursing students from the Honoris United Universities. Each student performed the VC on both the manikin's arm and the SP in random order. The main outcome measure was successful of VC after the second attempt. The secondary outcome measures were time to successful of VC, number of attempts, adherence to asepsis (Registered protocol number: PACTR202111766112898). ResultsOne hundred sixty learners were needed (α = β = 5%, 20% difference between the two techniques and 53% for SC). We enrolled 172 students. No statistical difference was found concerning the main outcome measure: 135 (78.5%) versus 138 (80.2%) for respectively LFS versus SP (p:0.689), nor for the secondary outcome measures. Six out of nine non-technical skills variables had a statistically significant difference in favor of SP. ConclusionNo statistical difference was found concerning the main and secondary outcome measures. RegistrationRegistered protocol number: Pan African Clinical Trials register (PACTR202111766112898)—Date of first recruitment on February 2, 2022.