Abstract Background Little information is available regarding the controversial issue of steroid withdrawal following heart transplantation (HT), or instead in the incidence of adverse steroid effects at dosages typically employed in Spain. Methods We analyzed the 5-year follow-up records of 1209 patients (82.5% men, aged ≥18 years) who underwent HT between 2000 and 2005 and survived at least 1 month in 13 Spanish centers. The incidences of first steroid withdrawal before 1, 3, and 5 years post-HT were expressed as Kaplan-Meier probability estimates. Three patient groups defined in accordance with steroid dosage at 1-year follow-up (0, ≤5, and >5 mg/d; groups A, B, and C, respectively) were compared with regard to the incidence of de novo hypertension, diabetes, and bone fractures over the following 2 years. Results The 5-year incidence of withdrawal was 28%, 21% of whom required reintroduction of steroids. Kaplan-Meier probabilities of withdrawal before 1, 3, and 5 years post-HT were 8.8% (95% confidence interval ([CI] 7.3%–10.7%), 27.8% (CI 25.2%–30.6%), and 30.2% (CI 27.5%–33.2%), respectively. At 1-year follow-up, 9.9% of patients were steroid-free, 28.9% were taking ≤5 mg/d, and 61.3% >5 mg/d. The 2-year incidence of de novo hypertension increased significantly (P = .012) from 13.5% to 29.6% to 35.3% in groups A, B, and C respectively. These groups did not differ significantly in regard to the 2-year incidence of diabetes or bone fractures. Conclusions Reintroduction of steroids was required by 21% of the 28% of Spanish HT patients who has been weaned from steroids within 5 years of HT. The incidence of de novo hypertension between 1 and 3 years post-HT increased with steroid dosage at 1-year follow-up. De novo diabetes and bone fractures showed no similar significant association.