The WhatsApp smartphone app is the most widely used instant messaging app in the world. Recent studies reported the use of WhatsApp for educational purposes, but there is no prospective study comparing WhatsApp's pedagogical effectiveness to that of any other teaching modality. The main objective of this study was to measure the impact of a learning program via WhatsApp on clinical reasoning in medical residents. This prospective, randomized, multicenter study was conducted among first- and second-year anesthesiology residents (offline recruitment) from four university hospitals in France. Residents were randomized in two groups of online teaching (WhatsApp and control). The WhatsApp group benefited from daily delivery of teaching documents on the WhatsApp app and a weekly clinical case supervised by a senior physician. In the control group, residents had access to the same documents via a traditional computer electronic learning (e-learning) platform. Medical reasoning was self-assessed online by a script concordance test (SCT; primary parameter), and medical knowledge was assessed using multiple-choice questions (MCQs). The residents also completed an online satisfaction questionnaire. In this study, 62 residents were randomized (32 to the WhatsApp group and 30 to the control group) and 22 residents in each group answered the online final evaluation. We found a difference between the WhatsApp and control groups for SCTs (60% [SD 9%] vs 68% [SD 11%]; P=.006) but no difference for MCQs (18/30 [SD 4] vs 16/30 [SD 4]; P=.22). Concerning satisfaction, there was a better global satisfaction rate in the WhatsApp group than in the control group (8/10 [interquartile range 8-9] vs 8/10 [interquartile range 8-8]; P=.049). Compared to traditional e-learning, the use of WhatsApp for teaching residents was associated with worse clinical reasoning despite better global appreciation. The use of WhatsApp probably contributes to the dispersion of attention linked to the use of the smartphone. The impact of smartphones on clinical reasoning should be studied further.