The negative impact of the COVID-19 pandemic on mental health has been extensively documented, while its possible positive impact on the individual, defined as Post-Traumatic Growth (PTG), has been much less investigated. The present study examines the association between PTG and socio-demographic aspects, pre-pandemic psychological adjustment, stressors directly linked to COVID-19 and four psychological factors theoretically implicated in the change processes (core belief violation, meaning-making, vulnerability and mortality perception). During the second wave of the pandemic 680 medical patients completed an online survey on direct and indirect COVID-19 stressors, health and demographic information, post-traumatic growth, core belief violation, meaning-making capacity, feelings of vulnerability and perceptions of personal mortality. Violation of core beliefs, feelings of vulnerability and mortality, and pre-pandemic mental illness positively correlated with post-traumatic growth. Moreover, the diagnosis of COVID-19, stronger violation of core beliefs, greater meaning-making ability, and lower pre-existing mental illness predicted greater PTG. Finally, a moderating effect of meaning-making ability was found. The clinical implications were discussed.