Serious illness communication is a key element of high-quality care, but it is difficult to implement in practice. The Serious Illness Care Program (SICP) is a multifaceted intervention that contributes to more, earlier, and better serious illness conversations and improved patient outcomes. This qualitative study examined the organizational and implementation factors that influenced improvement in real-world contexts. The authors performed semistructured interviews of 30 health professionals at five health systems that adopted SICP as quality improvement initiatives to investigate the organizational and implementation factors that appeared to influence improvement. After SICP implementation across the organizations studied, approximately 4,661 clinicians have been trained in serious illness communication and 56,712 patients had had an electronic health record (EHR)-documented serious illness conversation. Facilitators included (1) visible support from leaders, who financially invested in an implementation team and champions, expressed the importance of serious illness communication as an institutional priority, and created incentives for training and documenting serious illness conversations; (2) EHR and data infrastructure to foster performance improvement and accountability, including an accessible documentation template, a reporting system, and customized data feedback for clinicians; and (3) communication skills training and sustained support for clinicians to problem-solve communication challenges, reflect on communication experiences, and adapt the intervention. Inhibitors included leadership inaction, competing priorities and incentives, variable clinician acceptance of EHR and data tools, and inadequate support for clinicians after training. Successful implementation appeared to rely on multilevel organizational strategies to prioritize, reward, and reinforce serious illness communication. The insights derived from this research may function as an organizational road map to guide implementation of SICP or related quality initiatives.