Clinicians commonly use nonindicated (or "off-label") medications for the treatment of alcoholism, although there is no clear evidence to support this practice. Quetiapine and trazodone are 2 medications frequently used in this manner, especially to treat sleep disturbance associated with alcohol withdrawal. Using national administrative data from the Department of Veterans Affairs, we compared the differences among these medications in time to rehospitalization after discharge from an index hospitalization for alcohol dependence. Our outcome measure was the difference in time (weeks) to rehospitalization for patients given medications in 1 of 4 groups: quetiapine alone (median, 6.1 weeks); trazodone alone (median, 10.1 weeks); quetiapine combined (median, 7.1 weeks); and trazodone combined (median, 10.3 weeks) with other frequently used psychotropic drugs. Differences between groups were examined with Cox's proportional hazards regression using trazodone in combination with other medications as the reference category. Crude hazard ratios were determined first and then adjusted for covariates. There was no difference in the risk of rehospitalization when patients using quetiapine in combination were compared with the reference category (hazard ratio [HR] = 1.08; confidence interval [CI], 0.99-1.17; P < 0.0936). In contrast, when quetiapine was used alone there was a significantly higher risk of rehospitalization (HR = 1.22; CI = 1.06-1.41; P < 0.005). When trazodone was used alone there was no difference in risk in the unadjusted analysis (HR = 1.05; CI = 0.96-1.14; P < 0.3076); however, the HR increased to a significant level after adjusting for covariates (HR, 1.14; CI = 1.05-1.24; P < 0.0029) and for those with 2+ previous discharges (HR = 1.25; CI = 1.14-1.37; P < 0.0001). These findings suggest the need for additional studies to better understand what symptoms of alcoholism benefit from the use of these medications, at what dose levels, and with what other medication combinations.