Objectives: to analyze the relationship between the nursing practice environment and hospital sociotechnical complexity as perceived by nurses. Methods: a sequential explanatory mixed-methods study was conducted in a hospital in southern Brazil. The Brazilian version of the Practice Environment Scale-Nursing Work Index and the Complexity Characterization Questionnaire were administered to 132 nurses. Subsequently, semi-structured interviews were conducted with 18 participants, and the data were subjected to thematic analysis. Data integration was achieved through a connection approach. Results: the nursing practice environment was found to be favorable, except in the subscale concerning Staffing and Resource Adequacy, where complexity was present in the activities. The three emerging categories explained human and technical aspects related to complexity in the practice environment, quality of care, and patient safety. Unexpected variability was inversely correlated with the practice environment. Conclusions: the study results indicate a relationship between these constructs, with implications for the quality and the safety of care.