Despite angioscopy being used for more than 10 years, data regarding the prognostic significance are still limited. This study evaluated the prognostic relevance of the angioscopic lesion morphology and plaque colour on restenosis rate following coronary angioplasty. Out of 66 patients with coronary angioscopy prior to an angioplasty procedure, 46 patients with successful balloon dilation and 16 patients with stenting were included into the study. Angioscopic plaque morphology and plaque colour were correlated with the anginal status, the angiographic lesion morphology, the procedural result, and the restenosis rate during six months follow-up. Clinical follow-up was obtained from all patients, re-angiography was performed in 61%. Angioscopically complicated lesions were more frequent in patients with unstable versus stable angina (63% versus 28%, p < 0.005) and ACC/AHA type B2/C versus A/B1 stenoses (86% versus 7%, p < 0.03). In addition yellow plaques were more often seen in unstable versus stable angina (80% versus 50%, p < 0.02) and in type B2/C versus A/B1 lesions (81% versus 47%, p < 0.005). There were no deaths or myocardial infarctions during follow-up. Restenosis (n = 11) occurred significantly more frequent in patients with smooth, yellow lesions (37%) compared to all other lesion morphologies (9%, p < 0.02). Logistic regression analysis revealed angioscopically smooth, yellow plaques (p < 0.05) and angiographically type B2/C lesions (p < 0.03) as independent predictors for restenosis. We conclude that angioscopically smooth, yellow plaques covered by an intact inner vessel surface are associated with a higher incidence of restenosis following coronary angioplasty, potentially indicating a higher proliferative response after a mechanical trauma of such lesions.