Background: The clinical-epidemiological differences between primary infections versus reinfections of covid-19 with the 4th dose of bivalent mRNA vaccine are not known. Objective: Compare primary infections versus reinfections of covid-19 with 4th dose of bivalent mRNA vaccine. Methodology: An observational, longitudinal and prospective case series study of adult patients with covid-19 infections in vaccinated people with 4th dose in general medicine from October 1, 2022 to October 1, 2023. Descriptive epidemiological analysis considered a set of selected demographic and clinical features. Results: 16 people with fourth dose and with covid-19 infections and 5 people with fourth dose and with covid-19 reinfections from October 2022 to October 2023 were included. Reinfection versus primary infections were more frequent in women, socialhealth care workers, complex family, moderate-severe severity of infection, chronic diseases of the Neoplasms, Endocrine, Musculo-skeletal and Genitourinary groups, and presented more ENT and neurological symptoms. But, the only variable with statistically significant differences was the presence of Neoplasms (13% versus 0%; Fisher exact test = 0.0483). Conclusion: In the context of a general medicine consultation in Toledo (Spain) from October 2022 October 2023, in people with the fourth dose of bivalent mRNA vaccine against covid-19, covid-19 reinfections did not differ in their clinicalepidemiological characteristics except for being more frequent in presumably immunosuppressed patients (patients with Neoplasms) compared to covid-19 primary infections. In any case, our results, although consistent with the existing literature, should be taken with caution due to the small number of covid-19 cases included.