At a time where high levels of stress are reported in the veterinary profession, this study explores the challenges that veterinary graduates encounter when they enter general (first opinion) practice. Participants had written reflective accounts of their 'Most Puzzling Cases' for the postgraduate Professional Key Skills module of the Certificate in Advanced Veterinary Practice, offered by the Royal Veterinary College. Reasons that a case was puzzling, or became challenging, were thematically analysed. Fifteen summaries were analysed. Three core themes were identified: 'clinical reasoning', centred on the limitations of pattern recognition and the methods used to overcome this; the 'veterinary healthcare system', focusing on the need for continuity of care, time pressure and support in the transition to practice; and the 'owner', looking at the broader clinical skills needed to succeed in general practice. Clinical reasoning was raised as an issue; discussion of when pattern recognition is not appropriate and what to do in these cases was common. A lack of experience in general practice case types, and how to best operate in the resource-constrained environment in which they present, is the likely cause of this, suggesting that a greater focus on the primary care paradigm is needed within veterinary education. © British Veterinary Association (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.