The purpose of this study was to examine whether published findings regarding the association of personality disorders (PDs) with the persistence of substance use disorders (SUDs) are attributable to an artifact due to time of assessment of the PD. Two previous studies analyzed data from the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC) and found that Antisocial PD, Schizotypal PD, and Borderline PD are unique predictors of SUDs. However, a design limitation in NESARC (assessment of PDs at different waves) can potentially compromise these findings. To assess the influence of time of assessment of PDs and to identify associations that might be robust to time of assessment, we compared the association of PDs with 2 estimates of SUD persistence that were based on different populations at risk: (a) among those who were diagnosed with SUD at baseline, the proportion who continued to meet full criteria at follow-up ("prediction"); and (b) among those who were diagnosed with SUD at follow-up, the proportion who met full criteria at baseline ("postdiction"). Differences between prediction and postdiction revealed a robust pattern of higher odds ratios for postdiction among PDs assessed at baseline, and lower odds ratios for postdiction among PDs assessed at follow-up. All published significant associations between PDs and persistence of SUDs became nonsignificant in the postdiction analyses, with the exception of obsessive-compulsive PD predicting nicotine dependence persistence. The present results raise serious doubts about the validity of published findings on PDs and SUD persistence from the NESARC. Design limitations in NESARC preclude a direct comparison among PDs measured at different waves.