The study analyzed data from the electronic health records of 445,738 patients with COVID-19 as of April 1, 2022, who were eligible for Paxlovide treatment because of the risk of a severe course. It used target study emulation with six sequential trials during a 5-day treatment delay period and followed the incidence of PASC (Long COVID) at 180 days. Paxlovide treatment had no significant effect on the overall incidence of PASC or respiratory symptoms. It showed a small protective effect against cognitive symptoms (RR 0.91; 95% CI 0.84–0.98; p=0.019) and fatigue (RR 0.94; 95% CI 0.90–0.98; p=0.002). There was a small protective effect on PASC in patients aged 65+ years (RR 0.92; 95% CI 0.88–0.97; p<0.001; absolute risk difference ARD −0.43%; number needed to treat NNT 233) and those with a Charlson comorbidity index of 3 or 4 (ARD −1.30%). The main limitation is the assumption of controlling for all confounding variables. The conclusion of the study states that Paxlovid is probably not a definitive solution for the prevention of PASC.