SummaryCentral venous catheters (CVC) are commonly used to deliver daily intravenous medications to patients with AIDS, and CVC-associated bacterial infections have been a cause of substantial morbidity in such patients. Although previous studies have reported rates of CVC-associated infections in AIDS patients, none has compared rates by type of intravenous drug regimen used or by whether CVCs were percutaneously placed or tunneled under the skin. The charts of all AIDS patients diagnosed with cytomegalovirus (CMV) end-organ disease at San Francisco General Hospital between 1985 and 1990 were reviewed for evidence of CVC use and CVC-associated infection. Infection rates and time to infection were analyzed for serious CVC-associated infections (requiring catheter removal or hospitalization for intravenous antibiotic therapy) by type of anti-CMV therapy administered (ganciclovir versus foscarnet) and by type of CVC (tunneled versus percutaneous placement). Fifty-four patients had 72 CVCs in use for 11,622 days of intravenous anti-CMV therapy. There were 36 CVC-associated infections of which 23 were categorized as serious (rate, 0.20/100 catheter days). In patients receiving either ganciclovir or foscarnet therapy, we found no significant difference in serious infection rates or in infection-free survival time (216 vs. 282 days, p = 0.7). However, serious CVC infection-free time was significantly longer in patients with tunneled than with percutaneous CVCs (419 vs. 195 days, p = 0.018). The use of ganciclovir compared to foscarnet in the treatment of AIDS-related CMV disease was not associated with a greater risk of serious catheter-related infection. However, a lower risk of serious CVC-associated infections was observed in patients with tunneled versus percutaneous CVC placement.