• Prisoners are at-risk of self-harm during incarceration.
• Observable risk factors occurring during incarceration were most strongly associated with risk.
• Such risk factors may offer direction for self-harm prevention strategies.
Prisoners are at risk of self-harm during incarceration, yet national estimates of the rate and risk factors of self-harm are rare. We aimed to examine the rate and risk factors of self-harm on aggregate and by sex using a national population-based study design. Israel Prison Service data were examined on all persons incarcerated for a criminal offense 2009–2015 (N = 263,794). Self-harm was ascertained from real-time recorded observations. The study covariates were: demographic, criminal history, and prison environment factors. The association between the risk of self-harm and study covariates was estimated with relative risks and their corresponding 95% confidence intervals fitted with a Poisson regression model. During the seven-year study period of 237,945 (91%) males and 25,849 (9%) females, 1761 inmates (0.7%) inflicted self-harm. In the total population, among females and males the relative risk of self-harm was statistically significantly (FDR P < 0.05) consistently associated with: involvement in prison misconduct, violent behavior, and verbal threats of self-harm. Risk factors that occur during incarceration may offer immediate information to assess the risk of self-harm and to develop prevention strategies.