Rotavirus infection remains a major cause of mortality in children less than 5 years old, we now have live attenuated orally administered rotavirus vaccines in more than 112 countries. There is some evidence that in areas of high mortality, some vaccines may not be so effective and of course, there may be difficulties in accessing the vaccines in some low to middle income countries. In The Lancet Infectious Diseases, a paper from Bangladesh and one from India, present further evidence to help improve the likelihood of a successful programme, given these challenges. Kanungo S et al [Lancet Infectious Diseases 2022;22:1191–1199 https://doi.org/10.1016/S1473-3099(22)00161-X] have examined the safety and efficacy of two commonly available rotavirus vaccine preparations administering them in an interchangeable dosing schedule in an open label open-label, randomised, controlled, non-inferiority trial. They recruited 1979, healthy 6–8 week old infants who infants were randomly assigned into six groups. Two groups in a single regimen and four groups in a mixed vaccine regimen. The non-inferiority margin was set at 10%. The sero-response rate in the mixed vaccine regimen group (33·5% [95% CI 30·9–36·2]) was non-inferior compared with the single vaccine regimen group (29·6% [26·1–33·4]); the sero -response rate difference was 3·9% (95% CI −0·7 to 8·3). The proportion of participants with any type of solicited adverse events was 90·9% (95% CI 88·4–93·0) in the single vaccine regimen group and 91·1% (89·5–92·6) in the mixed vaccine regimen group. No vaccine-related serious adverse events or intussusception were reported during the study. So a single vaccine regimen can be interchangeable with a mixed vaccine regimen. In a head-to-head comparison of the immunogenicity of two of the commonly available rotavirus vaccines, Velasquez-Portocarrero DE et al [Lancet Infectious Diseases 2022 https://doi.org/10.1016/S1473-3099(22)00368-1] completed a randomised, controlled, open-label, parallel trial carried out in Bangladesh. They enrolled a total of 1144 infants who were randomly assigned to one of the two vaccine arms; n=571 on one group and n=573 in the other. Rotavirus IgA seroconversion, 4 weeks after the full series occurred in 390 (73%) of 531 infants age 18 weeks in one arm and 354 (64%) of 549 infants age 14 weeks in the other arm (p=0·01). There were other comparisons at different times after the vaccines with similar differences. Essentially, one of these vaccines induced a higher magnitude and longer duration of rotavirus IgA response than the other vaccine. So it is important to recognise that in this particular setting some vaccine may not be as effective as others. These two papers illustrate the importance of carrying out studies in the countries where mortality is the highest and diseases like gastroenteritis are most prevalent. Future vaccination strategies need to be aware of differences in performance of different vaccines in these settings but also be reassured that a mixed dosing regimen will allow for flexibility in administering the vaccines. This may help to overcome vaccine shortages and supply chain issues, and targeting migrant populations more readily.