Computer keyboards may contribute to patient infections. We cultured new keyboards, with/without keyboard covers, before placing them in adult inpatient rooms and recultured after 6 months. Nonpathogenic bacteria were present initially but potentially pathogenic bacteria were cultured only after use. Coagulase negative Staphylococcus colonization increased after use (P < .001). Keyboards with a cover had more potentially pathogenic bacteria (22% vs 16%), which although not significant statistically (P = .72), likely due to sample size, trended against covers offering protection.