Drug use among parenting women is a significant risk factor for a range of negative child outcomes, including exposure to violence, child maltreatment, and child behavior problems. Implementation of brief interventions with this population may be greatly facilitated by computer-based interventions. Randomized clinical trial with 4-month follow-up. Participants were 107 postpartum women recruited from an urban obstetric hospital primarily serving a low-income population. Women were randomized into assessment only versus assessment plus brief intervention conditions; 76 (71%) returned for follow-up evaluation. A 20-minute, single-session, computer-based motivational intervention (based on motivational interviewing methods), combined with two nontailored mailings and voucher-based reinforcement of attendance at an initial intake/treatment session. Illicit drug use as measured by qualitative urinalysis and self-report. Frequency of illicit drug use other than marijuana increased slightly for the control group, but declined among intervention group participants (p<0.05, between-group Mann-Whitney U; d=0.50); the magnitude of intervention effects on changes in marijuana use frequency was similar, but did not reach statistical significance. Point-prevalence analysis at follow-up did not show significant group differences in drug use. However, trends under a range of assumptions regarding participants lost to follow-up all favored the intervention group, with most effect sizes in the moderate range (odds ratios 1.4 to 4.7). Results tentatively support the efficacy of this high-reach, replicable brief intervention. Further research should seek to replicate these findings and to further develop the computer as a platform for validated brief interventions.