BACKGROUND: Massive screening campaigns for SARS-CoV-2 are currently carried out throughout the world, relying on reverse-transcriptase-polymerase chain reaction (RT-PCR) following nasopharyngeal swabbing performed by a healthcare professional. Yet, due to the apprehension of pain induced by nasopharyngeal probing, poor adhesion to those screening campaigns can be observed. To enhance voluntary participation and to avoid unnecessary exposition to SARS-CoV-2, self-swabbing could be proposed. To date, no data have been published concerning pain induced by conventional- or self-swabbing. Thus, the primary objective of the present study was to evaluate pain induced with the conventional swabbing method and compare it to self-swabbing. Secondary objectives focused on swabbing-induced discomfort and acceptability of the two methods. METHODS: The study was conducted in Clermont-Ferrand medical school (France). Overall, 190 students were randomised into two groups and experienced either self- or conventional-swabbing. Each subject had to rate pain, discomfort and acceptability of such swabbing on a 0-10 numeric rating scale. RESULTS: No significant difference was found between the two methods. The mean pain level was 2.5 ± 1.9, 28% rating pain as ≥4/10. Discomfort was 4.8 ± 2.2, 66% indicating significant (≥4/10) discomfort. Higher pain and discomfort were associated with female sex. Acceptability was ≥8/10 for 89.0% of the subjects and all would have accepted to undergo a new test with the same technique if necessary. CONCLUSION: Both conventional and self-swabbing induce low levels of pain for most young healthy volunteers whereas discomfort is very frequent. Nonetheless, both methods are indifferently well-accepted in medical students. Future studies amongst symptomatic subjects are awaited. SIGNIFICANCE: Using the thinnest available swabs, procedural pain induced by nasopharyngeal swabbing for SARS-CoV-2 screening is very low for most subjects and should not limit voluntary participation in screening campaigns. Self-swabbing does not lead to more pain or discomfort compared to conventional swabbing, is well-accepted, and could be proposed to optimize screening campaigns, at least in healthcare professionals.