We conducted a prospective randomized study to investigate predictive factors for short- and long-term outcome of anterior cervical decompression and fusion (ACDF) as measured by current pain intensity on the Visual Analogue Scale (VAS) and by disability using the Neck Disability Index (NDI). Current understanding about how preoperative and short-term outcome data predict long-term outcome is sparse, and there are few studies involving analysis of short-term follow-up using multivariate approaches with quantification of the relative importance of each variable studied. A total of 95 patients were randomly allocated for ACDF with the cervical intervertebral fusion cage or the Cloward procedure. The mean follow-up time was 19 months (range 12-24) for short-term follow-up and 76 months (range 56-94 months) for long-term. Background factors, radiologically detected findings, physiological measurements, treatment type, pain, and disability were used as potential predictors. Multivariate statistical analysis by projection to latent structures was used to investigate predictors of importance for short- and long-term outcome of ACDF. A "preoperative" low disability and pain intensity, non-smoking status, male sex, good hand strength, and an active range of motion (AROM) in the neck were significant predictors for good short- and long-term outcomes. The short-term outcome data were better at predicting long-term outcome than were baseline data. Radiologically detected findings and surgical technique used were mainly insignificant as predictors. We suggest that the inclusion criteria for ACDF should be based on a bio-psycho-social model including NDI. NDI may also be regarded as an important outcome measurement in evaluation of ACDF.