Objectives To investigate the relationships between patient safety culture (PSC) dimensions and PSC self-reported outcomes across different cultures and to gain insights in cultural differences regarding PSC. Design Observational, cross-sectional study. Setting Ninety Belgian hospitals and 13 Palestinian hospitals. Participants A total of 2836 healthcare professionals matched for profession, tenure and working hours. Primary and secondary outcome measures The validated versions of the Belgian and Palestinian Hospital Survey on Patient Safety Culture were used. An exploratory factor analysis was conducted. Reliability was tested using Cronbach’s alpha (α). In this study, we examined the specific predictive value of the PSC dimensions and its self-reported outcome measures across different cultures and countries. Hierarchical regression and bivariate analyses were performed. Results Eight PSC dimensions and four PSC self-reported outcomes were distinguished in both countries. Cronbach’s α was α≥0.60. Significant correlations were found between PSC dimensions and its self-reported outcome (p value range <0.05 to <0.001). Hierarchical regression analyses showed overall perception of safety was highly predicted by hospital management support in Palestine (β=0.16, p<0.001) and staffing in Belgium (β=0.24, p<0.001). The frequency of events was largely predicted by feedback and communication in both countries (Palestine: β=0.24, p<0.001; Belgium: β=0.35, p<0.001). Overall grade for patient safety was predicted by organisational learning in Palestine (β=0.19, p<0.001) and staffing in Belgium (β=0.19, p<0.001). Number of events reported was predicted by staffing in Palestine (β=−0.20, p<0.001) and feedback and communication in Belgium (β=0.11, p<0.01). Conclusion To promote patient safety in Palestine and Belgium, staffing and communication regarding errors should be improved in both countries. Initiatives to improve hospital management support and establish constructive learning systems ...