Background: Joiner’s interpersonal theory of suicide (IPTS) proposes that suicide results from the combination of a perception of burdening others, social alienation, and the capability for self-harm. The theory gained some empirical support, however the overall model has yet to be tested. This study aimed to test the main predictions of IPTS in a large community sample of Israeli adolescents. Method: 1196 Israeli Jewish and Arab high-school pupils participating in the SEYLE project completed a self-report questionnaire measuring perceived burdensomeness, thwarted belongingness, health risk behaviors, and non-suicidal self-injury (risk variables), and suicidal ideation and suicide attempts (outcome measures). The data were tested in cross-sectional regression models. Results: Consistent with IPTS, perceived burdensomeness was found to interact with thwarted belongingness, predicting suicidal ideation. Depression mediated most of the effect of thwarted belongingness and perceived burdensomeness on suicidal ideation. Acquired capability for self-harm, as measured by health risk behaviors and direct non-suicidal self-injurious behaviors, predicted suicide attempt. However, this mechanism operated independently from ideation rather than in interaction with it, at variance with IPTS-based predictions. Limitations: The cross-sectional design precludes conclusions about causality and directionality. Proxy measures were used to test the interpersonal theory constructs. Conclusion: The findings support some of the IPTS predictions but not all, and imply two separate pathways for suicidal behavior in adolescents: one related to internalizing psychopathology and the other to self-harm behaviors. This conceptualization has clinical implications for the differential identification of adolescents at risk for suicidal behavior and for the development of prevention strategies.