Introduction The unalleviated burden of chronic physical illness (CPI) increases the risk of suicidal behaviors (SB) in affected individuals. This study tested the interpersonal theory of suicide (ITS) in patients with CPI. Methods Patients diagnosed with cardiovascular, cerebrovascular, and renal diseases were recruited from two hospitals in South Korea. Data from 257 participants who completed Time (T) 1 and T2 surveys were analyzed. Hierarchical regression analyses for passive and active suicide ideation (PSI and ASI), and suicide plans and attempts (SP and SA) at both time points were conducted. Results Interpersonal theory of suicide hypotheses were partially supported. Even accounting for factors such as depression, anxiety, and lifetime SA, some main and interaction effects of the ITS constructs explained SB in a cross-sectional examination, but to a lesser degree in a longitudinal examination that controlled for T1 SB. PB was a consistent correlate of SB. TB was also relevant, as PB–SA association was significant among participants with high TB both times. ASI was associated with SP and SA at T1, and the ASI-SP association at T1 was stronger at a high CS level. Conclusions Overall, the results suggest the relevance of ITS constructs that warrant attention to prevent SB in patients with CPI.