Background: Responding to online patient feedback is considered integral to patient safety and quality improvement. However, guidance on how to respond effectively is limited, with limited attention paid to patient perceptions and reactions. Objectives: To identify factors considered potentially helpful in enhancing response quality; coproduce a best-practice response framework; and quality-appraise existing responses. Design: A four-stage mixed methodology: (i) systematic search of stories published on Care Opinion about adult mental health services in the South West of England; (ii) collaborative thematic analysis of responses to identify factors potentially helpful in enhancing response quality; (iii) validation of identified factors by a patient-carer group (n = 12) leading to the coproduction of a best-practice response framework; and (iv) quality appraisal of existing responses. Results: A total of 245 stories were identified, with 183 (74.7%) receiving a response. Twenty-four (9.8%) had been heard but not yet responded to. 1.6% (n = 4/245) may lead to a change. Nineteen factors were considered influential in response quality. These centred around seven subject areas: (i) introductions; (ii) explanations; (iii) speed of response; (iv) thanks and apologies; (v) response content; (vi) signposting; and (vii) response sign-off that were developed into a conceptual framework (the Plymouth, Listen, Learn and Respond framework). Quality appraisal of existing responses highlighted areas for further improvement demonstrating the framework's utility. Conclusion: This study advances existing understanding by providing previously unavailable guidance. It has clear practical and theoretical implications for those looking to improve health-care services, patient safety and quality of care. Further validation of the conceptual framework is encouraged.