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Abstract Background There is growing recognition of the psychological impact of adversity associated with armed conflict on exposed civilian populations. Yet there is a paucity of evidence on the value of mental health programs in these contexts, and of the chronology of psychological sequelae, especially in prolonged conflicts with repeated cycles of extreme violence. Here, we describe changes in the psychological profile of new patients in a mental health program after the military offensive Cast Lead, in the context of the prolonged armed conflict involving the Gaza Strip. Methods This study analyses routinely collected program data from a Médecins Sans Frontières mental health program in the Gaza Strip spanning 2007–2011. Data consist of socio-demographic as well as clinical baseline and follow-up data on new patients entering the program. Comparisons were made through Chi square and Fisher’s exact tests, univariate and multivariate logistic and linear regression. Results PTSD, depression and other anxiety disorders were the most frequent psychopathologies, with 21% having multiple diagnoses. With a median of nine sessions, clinical improvement was recorded for 83% (1122/1357), and more common for those with separation anxiety, acute and posttraumatic disorders as principal diagnosis (855/1005), compared to depression (141/183, p Conclusion Evolving changes in patient volume, diagnoses and recall period to triggering events suggest a lengthy and durable effect of an intensified exposure to violence in a context of prolonged conflict. Our findings suggest that mental health related humanitarian relief in protracted conflicts might need to prepare for an increase in patients with changing profiles over an extended period following an acute flare-up in violence.