Objective: Medical errors or near misses (MENM) may cause serious negative outcomes for the patients. However, medical professionals with MENM may also be secondary victims. Although the association between MENM and depression among medical professionals has been explored in several previous studies, the possible causal relationship has been explored less, especially in China. In this study, our first aim was to determine the prevalence of MENM among Chinese medical professionals. We also wanted to explore the causal effect of MENM on depressive symptoms based on a propensity-score matching analysis. Methods: A cross-sectional study was conducted among medical professionals in Chinese public general hospitals, and 3426 medical professionals were analyzed in this study. The Center for Epidemiologic Studies Depression (CES-D) scale was used to assess depressive symptoms. Social support was measured by the Multidimensional Scale of Perceived Social Support (MSPSS). MENM, social-demographic variables, occupational characteristics, and physical disease were also evaluated in this study. Results: The one-year prevalence of perceived MENM was 2.9% among medical professionals in Chinese public general hospitals. The results of logistic regressions showed that working hours/week (OR = 1.02, p < 0.05) and depressive symptoms (OR = 1.05, p < 0.001) were associated with MENM. After propensity score matching, depressive symptoms were associated with MENM (OR = 1.05, p < 0.001) among medical professionals. The associations between occupational characteristics, physical disease, social support, and MENM were not supported by this study. Conclusions: The one-year prevalence of MENM was low in Chinese public general hospitals, and based on our propensity score matching analyses, the occurrence of MENM may cause depressive symptoms in medical professionals. A bigger effort by health systems and organizations may be helpful for reducing MENM.