Objective: To evaluate the screening effectiveness of speculoscopy, a magnified chemiluminescent visual examination combined with the Papanicolaou smear as compared with the Papanicolaou smear alone. Methods: This was a prospective, practice-based study. The study participants were women aged 16–60 years who were regularly scheduled for Papanicolaou smears. All women were subject to a Papanicolaou smear and speculoscopy. Positive speculoscopy findings and/or Papanicolaou smear findings of a squamous intraepithelial lesion (SIL) were investigated further with colposcopy and biopsy. Results: A total of 5692 women were evaluated, and 799 (14%) were positive by one or both screening tests. Of the 410 biopsy specimens that were obtained, 32 showed high-grade SIL, 191 low-grade SIL, 145 reactive and reparative cells, and 42 were found to be within normal limits. The addition of speculoscopy to the routine Papanicolaou smear resulted in finding 11 of the 32 (34%) women with high-grade SIL and 154 of the 191 (81%) women with low-grade SIL. Conclusion: Speculoscopy, when combined with the Papanicolaou smear as a screening test, yields a higher percentage of women with biopsy-confirmed cervical pathology than the use of the Papanicolaou smear as a sole screening test.