AbstractThe definition of minimal relevant Pap smear abnormality is crucial for balancing the beneficial effects of screening (prevented mortality) with negative side‐effects (the high positivity rate). After inflammation ceased to be defined as a borderline abnormal smear outcome in The Netherlands in 1996, the proportion of these smears dropped from 10% to less than 2%. Because this may have caused a loss in smear sensitivity, we analysed the changes in the incidence of cervical cancer after a negative Pap smear. All negative smears made at ages 30–64 in 1990–1995 (n = 1,546,252) and 1998–2006 (n = 3,552,716), registered in the national registry of histo‐ and cytopathology (PALGA), were followed for up to 9 years. During follow‐up of the 1990–1995 smears, 377 women developed cervical cancer within 5,232,959 woman‐years at risk, while during the follow‐up of the 1998–2006 smears, 619 women developed cervical cancer within 11,210,675 woman‐years at risk. The cumulative incidence after the definition change was not significantly higher than before: e.g. at 6 years, the cumulative incidence for smears made in 1990–1995 was 46 per 100,000 (95% CI: 41–52), and for smears in 1998–2006 was 48 per 100,000 (95% CI: 43–54), p = 0.59. The hazard ratio for 1998–2006 compared to 1990–1995 adjusted for age, number of previous negative smears and history of abnormalities was 0.90 (95% CI: 0.78–1.03). In The Netherlands, a setting with high‐quality cytological screening, treating smears with only signs of inflammation as negative leads to a considerably lower positivity rate without increasing the risk for cervical cancer after a negative smear. © 2008 Wiley‐Liss, Inc.