This study aimed to analyse and determine the risk factors of disease aggravation faced by older patients with non-communicable diseases (NCDs) and their interwoven correlations. We employed a descriptive and cross-sectional study, which followed the STROBE guidelines for reporting. We conducted a semi-structured in-depth interview with 26 older patients with NCDs from a hospital in Qingdao, China between July and August 2022 on the basis of the literature review. Then, we analysed data using the directed content analysis and determined risk factors through a focus group discussion and the Delphi consultation. Afterward, we combined interpretive structural modelling and hierarchical holographic modelling to construct a hierarchical structure model and drew relationship framework diagrams to exhibit diversified risk factors and complex interwoven correlations. We identified 30 risk factors from individual, interpersonal, organisational, community and policy levels. The hierarchical structure model constructed by interpretive structural modelling demonstrated a four-layer structure, and the individual and interpersonal levels were at the highest layer. The relationship framework diagrams demonstrated the identification process of risk factors and interwoven correlations at individual and organisational levels. Risk factors causing disease aggravation amongst older patients with NCDs are diverse. To delay the progression of NCDs, we should comprehensively explore risk factors, interpret the root causes and effects of risks from multiple perspectives and consider the interaction amongst multi-level risk factors to develop precise measures related to risk control. Controlling risk factors is an effective measure to postpone disease aggravation. Through this study, we provide a scientific and comprehensive basis for clinical risk screening so that healthcare providers can sense potential risk factors for disease aggravation in older patients' surroundings and formulate targeted nursing measures according to the risk factors faced by different patients. Patients participated in interviews to supplement risk factors included in our study. Experts provided opinions on the inclusion, exclusion and modification of risk factors.