Long-term adherence and persistence with any therapy are very poor ( approximately 50%). Adherence to therapy is defined as the percentage of prescribed medication taken, and persistence is defined as continuing to take prescribed medication. We examined whether monitoring by nursing staff could enhance adherence and persistence with antiresorptive therapy and whether presenting information on response to therapy provided additional benefit. In addition we evaluated the impact of monitoring on treatment efficacy. Seventy-five postmenopausal women with osteopenia were randomized to 1) no monitoring, 2) nurse-monitoring, or 3) marker-monitoring. All subjects were prescribed raloxifene. At 12, 24, and 36 wk, the nursing staff reviewed subjects in the monitored (nurse-monitoring or marker-monitoring) groups using a predefined protocol. The marker-monitored group were also presented a graph of response to therapy using percentage change in urinary N-telopeptide of type I collagen (uNTX), a bone resorption marker, at each visit. Biological response to therapy at 1 yr was determined using the percent change in bone mineral density (BMD) and uNTX. Treatment adherence and persistence were assessed using electronic monitoring devices. Survival analysis showed that the monitored group increased cumulative adherence to therapy by 57% compared with no monitoring (P = 0.04). There was a trend for the monitored group to persist with therapy for 25% longer compared with no monitoring (P = 0.07). Marker measurements did not improve adherence or persistence to therapy compared with nurse-monitoring alone. Adherence at 1 yr was correlated with percent change in hip (BMD) (r = 0.28; P = 0.01) and percent change in uNTX (r = -0.36; P = 0.002). In conclusion, monitoring of patients increased adherence to therapy by 57% at 1 yr. Increased adherence to therapy increased the effectiveness of raloxifene therapy determined using surrogate end points.