Psychiatric disorders and substance abuse are barriers that limit access to timely treatment and can lead to Potentially Preventable Hospitalizations (PPH). The aim of this study is to identify the role played by gender in the association between mental health and PPH. Hospital discharge records (HDRs) from the Local Health Authority of Pescara (Italy) from 2015 to 2021 were examined and PPH were measured according to Prevention Quality Indicators (PQIs) provided by the Agency for Healthcare Research and Quality. In total, 119,730 HDRs were eligible for the study and 21,217 patients fell into the PQI categories. Mental health disorders and addictions were extracted from the HDRs through the Elixhauser Enhanced ICD-9-CM algorithm. The association between PQI hospitalization and some predictors considered was evaluated with multivariate logistic regression models. In males and females, alcohol abuse showed a protective role towards preventable admissions for PQI-90 (all types of conditions) and PQI-92 (chronic conditions). In contrast, there is a gender gap in accessibility to primary health care, especially for acute conditions leading to PPH. Indeed, in males, PQI-91 admissions for acute conditions were found to be positively associated with drug abuse, psychosis, and depression, whereas this was not the case for females.