Objective: To evaluate 3 formulations of copper (Cu)-based self-sanitizing surfaces for antimicrobial efficacy and durability over 1 year in inpatient clinical areas and laboratories. Design: Randomized control trial. Setting: We assessed 3 copper formulations: (1) solid alloy 80% Cu-20% Ni (integral copper), (2) spray-on 80% Cu-20% Ni (spray-on) and (3) 16% composite copper-impregnated surface (CIS). In total, 480 coupons (1 cm2) of the 3 products and control surgical grade (AISI 316) stainless steel were inserted into gaskets and affixed to clinical carts used in patient care areas (including emergency and maternity units) and on microbiology laboratory bench work spaces (n = 240). The microbial burden and assessment of resistance to wear, corrosion, and material compatibility were determined every 3 months. Participants included 3 tertiary-care Canadian adult hospital and 1 pediatric-maternity hospital. Results: Copper formulations used on inpatient units statistically significantly reduced bacterial bioburden compared to stainless steel at months 3 and 6. Only the integral copper product had significantly less bacteria than stainless steel at month 12. No statistically significant differences were detected in microbial burden between copper formulations and stainless-steel coupons on microbiology laboratory benches where bacterial counts were low overall. All mass changes and corrosion rates of the formulations were acceptable by engineering standards. Conclusions: Copper surfaces vary in their antimicrobial efficacy after 1 year of hospital use. Frequency of cleaning and disinfection influence the impact of copper; the greatest reduction in microbial bioburden occurred in clinical areas compared to the microbiology laboratory where cleaning and disinfection were performed multiple times daily.